Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Whole tumour cell-based vaccines: tuning the instruments to orchestrate an optimal antitumour immune response

British Journal of Cancer volume 129, pages 572–585 (2023)Cite this article

Subjects

Abstract

Immunotherapy, particularly those based on immune checkpoint inhibitors (ICIs), has become a useful approach for many neoplastic diseases. Despite the improvements of ICIs in supporting tumour regression and prolonging survival, many patients do not respond or develop resistance to treatment. Thus, therapies that enhance antitumour immunity, such as anticancer vaccines, constitute a feasible and promising therapeutic strategy. Whole tumour cell (WTC) vaccines have been extensively tested in clinical studies as intact or genetically modified cells or tumour lysates, injected directly or loaded on DCs with distinct adjuvants. The essential requirements of WTC vaccines include the optimal delivery of a broad battery of tumour-associated antigens, the presence of tumour cell-derived molecular danger signals, and adequate adjuvants. These factors trigger an early and robust local innate inflammatory response that orchestrates an antigen-specific and proinflammatory adaptive antitumour response capable of controlling tumour growth by several mechanisms. In this review, the strengths and weaknesses of our own and others’ experiences in studying WTC vaccines are revised to discuss the essential elements required to increase anticancer vaccine effectiveness.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Whole tumour cell vaccine types.
Fig. 2: Types of tumour Ags present in allogeneic whole tumour cell vaccines.
Fig. 3: Strategies to induce adjuvanticity and immunogenicity of tumour cells used as a source of Ags in whole tumour cell vaccines.

Similar content being viewed by others

Data availability

Not applicable.

References

  1. Meric-Bernstam F, Larkin J, Tabernero J, Bonini C. Enhancing antitumor efficacy with immunotherapy combinations. Lancet. 2021;392:1010–22.

    Article  Google Scholar 

  2. Berraondo P, Sanmamed MF, Ochoa MC, Etxeberria I, Aznar MA, Pérez-Gracia JL, et al. Cytokines in clinical cancer immunotherapy. Br J Cancer. 2019;120:6–15.

    Article  CAS  PubMed  Google Scholar 

  3. Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, et al. T-cell transfer therapy targeting mutant KRAS in cancer. N Engl J Med. 2016;375:2255–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hossian AKMN, Hackett CS, Brentjens RJ, Rafiq S. Multipurposing CARs: same engine, different vehicles. Mol Ther. 2022;30:1381–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. van der Burg SH, Arens R, Ossendorp F, van Hall T, Melief CJ. Vaccines for established cancer: overcoming the challenges posed by immune evasion. Nat Rev Cancer. 2016;16:219–33.

    Article  PubMed  Google Scholar 

  6. Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375:1845–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pires da Silva I, Ahmed T, Reijers ILM, Weppler AM, Betof Warner A, Patrinely JR, et al. Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study. Lancet Oncol. 2021;22:836–47.

    Article  CAS  PubMed  Google Scholar 

  8. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bonaventura P, Shekarian T, Alcazer V, Valladeau-Guilemond J, Valsesia-Wittmann S, Amigorena S, et al. Cold tumors: a therapeutic challenge for immunotherapy. Front Immunol. 2019;10:168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Donninger H, Li C, Eaton JW, Yaddanapudi K. Cancer vaccines: promising therapeutics or an unattainable dream. Vaccines. 2021;9:668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017;547:217–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Calvo Tardón M, Allard M, Dutoit V, Dietrich PY, Walker PR. Peptides as cancer vaccines. Curr Opin Pharmacol. 2019;47:20–6.

    Article  PubMed  Google Scholar 

  13. Saxena M, van der Burg SH, Melief CJM, Bhardwaj N. Therapeutic cancer vaccines. Nat Rev Cancer. 2021;21:360–78.

    Article  CAS  PubMed  Google Scholar 

  14. Mustafa AS. BCG as a vector for novel recombinant vaccines against infectious diseases and cancers. Vaccines. 2020;8:736.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Raman SS, Hecht JR, Chan E. Talimogene laherparepvec: review of its mechanism of action and clinical efficacy and safety. Immunotherapy. 2019;11:705–23.

    Article  CAS  PubMed  Google Scholar 

  16. Chesney JA, Ribas A, Long GV, Kirkwood JM, Dummer R, Puzanov I, et al. Randomized, double-blind, placebo-controlled, global phase III trial of talimogene laherparepvec combined with pembrolizumab for advanced melanoma. J Clin Oncol. 2023;41:528–40.

    Article  CAS  PubMed  Google Scholar 

  17. Christopoulos PF. The future of tumor vaccines in the post-COVID-19 era-current challenges. Immun Inflamm Dis. 2021;9:1795–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Vandenberg L, Belmans J, Van Woensel M, Riva M, Van Gool SW. Exploiting the immunogenic potential of cancer cells for improved dendritic cell vaccines. Front Immunol. 2016;6:663.

    Google Scholar 

  19. Huang MN, Nicholson LT, Batich KA, Swartz AM, Kopin D, Wellford S, et al. Antigen-loaded monocyte administration induces potent therapeutic antitumor T-cell responses. J Clin Investig. 2020;130:774–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yewdall AW, Drutman SB, Jinwala F, Bahjat KS, Bhardwaj N. CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen-presenting cells. PLoS ONE. 2010;5:e11144.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Garg AD, Coulie PG, Van den Eynde BJ, Agostinis P. Integrating next-generation dendritic cell vaccines into the current cancer immunotherapy landscape. Trends Immunol. 2017;38:577–93.

    Article  CAS  PubMed  Google Scholar 

  22. Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2020;20:7–24.

    Article  CAS  PubMed  Google Scholar 

  23. Liu J, Fu M, Wang M, Wan D, Wei Y, Wei X. Cancer vaccines as promising immuno-therapeutics: platforms and current progress. J Hematol Oncol. 2022;15:28.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Baghdadi M, Nagao H, Yoshiyama H, Akiba H, Yagita H, Dosaka-Akita H, et al. Combined blockade of TIM-3 and TIM-4 augments cancer vaccine efficacy against established melanomas. Cancer Immunol Immunother. 2013;62:629–37.

    Article  CAS  PubMed  Google Scholar 

  25. Fan X, Quezada SA, Sepúlveda MA, Sharma P, Allison JP. Engagement of the ICOS pathway markedly enhances the efficacy of CTLA-4 blockade in cancer immunotherapy. J Exp Med. 2014;211:715–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA. 2010;107:4275–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Faries MB, Mozzillo N, Kashani-Sabet M, Thompson JF, Kelley MC, DeConti RC, et al. Long-term survival after complete surgical resection and adjuvant immunotherapy for distant melanoma metastases. Ann Surg Oncol. 2017;24:3991–4000.

    Article  PubMed  Google Scholar 

  28. Dillman RO, Cornforth AN, Nistor GI, McClay EF, Amatruda TT, Depriest C. Randomized phase II trial of autologous dendritic cell vaccines versus autologous tumor cell vaccines in metastatic melanoma: 5-year follow up and additional analyses. J Immunother Cancer. 2018;6:19.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Pulendran BS, Arunachalam P, O’Hagan DT. Emerging concepts in the science of vaccine adjuvants. Nat Rev Drug Discov. 2021;20:454–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nijen Twilhaar MK, Czentner L, Bouma RG, Olesek K, Grabowska J, Wang AZ, et al. Incorporation of Toll-like receptor ligands and inflammasome stimuli in GM3 liposomes to induce dendritic cell maturation and T cell responses. Front Immunol. 2022;13:842241.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sondak VK, Sosman JA. Results of clinical trials with an allogenic melanoma tumor cell lysate vaccine: Melacine. Semin Cancer Biol. 2003;13:409–15.

    Article  CAS  PubMed  Google Scholar 

  32. Petrovsky N. Comparative safety of vaccine adjuvants: a summary of current evidence and future needs. Drug Saf. 2015;38:1059–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Facciolà A, Visalli G, Laganà A, Di Pietro A. An overview of vaccine adjuvants: current evidence and future perspectives. Vaccines. 2022;10:819.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Iribarren K, Bloy N, Buqué A, Cremer I, Eggermont A, Fridman WH, et al. Trial watch: immunostimulation with Toll-like receptor agonists in cancer therapy. Oncoimmunology. 2015;5:e1088631.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Chiang CL, Kandalaft LE. In vivo cancer vaccination: which dendritic cells to target and how? Cancer Treat Rev. 2018;71:88–101.

    Article  CAS  PubMed  Google Scholar 

  36. Lin MJ, Svensson-Arvelund J, Lubitz GS, Marabelle A, Melero I, Brown BD, et al. Cancer vaccines: the next immunotherapy frontier. Nat Cancer. 2022;3:911–26.

    Article  CAS  PubMed  Google Scholar 

  37. Tanaka J, Sugimoto K, Shiraki K, Tameda M, Kusagawa S, Nojiri K, et al. Functional cell surface expression of toll-like receptor 9 promotes cell proliferation and survival in human hepatocellular carcinomas. Int J Oncol. 2010;37:805–14.

    CAS  PubMed  Google Scholar 

  38. Matijevic Glavan T, Cipak Gasparovic A, Vérillaud B, Busson P, Pavelic J. Toll-like receptor 3 stimulation triggers metabolic reprogramming in pharyngeal cancer cell line through Myc, MAPK, and HIF. Mol Carcinog. 2017;56:1214–26.

    Article  CAS  PubMed  Google Scholar 

  39. Escobar A, López M, Serrano A, Ramírez M, Pérez C, Aguirre A, et al. Dendritic cell immunizations alone or combined with low doses of interleukin-2 induce specific immune responses in melanoma patients. Clin Exp Immunol. 2005;142:555–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Laheru D, Lutz E, Burke J, Biedrzycki B, Solt S, Onners B, et al. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res. 2008;14:1455–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Comiskey MC, Dallas MC, Drake CG. Immunotherapy in prostate cancer: teaching an old dog new tricks. Curr Oncol Rep. 2018;20:75.

    Article  PubMed  Google Scholar 

  42. Larsen ES, Joensen UN, Poulsen AM, Goletti D, Johansen IS. Bacillus Calmette-Guérin immunotherapy for bladder cancer: a review of immunological aspects, clinical effects and BCG infections. APMIS. 2020;128:92–103.

    Article  PubMed  Google Scholar 

  43. Hsueh EC, Essner R, Foshag LJ, Ollila DW, Gammon G, O’Day SJ, et al. Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine. J Clin Oncol. 2002;20:4549–54.

    Article  CAS  PubMed  Google Scholar 

  44. Motl SE. Technology evaluation: Canvaxin, John Wayne Cancer Institute/CancerVax. Curr Opin Mol Ther. 2004;6:104–11.

    CAS  PubMed  Google Scholar 

  45. Mordoh A, Aris M, Carri I, Bravo AI, Podaza E, Pardo JCT, et al. An update of cutaneous melanoma patients treated in adjuvancy with the allogeneic melanoma vaccine VACCIMEL and presentation of a selected case report with in-transit metastases. Front Immunol. 2022;13:842555.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ragupathi G, Livingston PO, Hood C, Gathuru J, Krown SE, Chapman PB, et al. Consistent antibody response against ganglioside GD2 induced in patients with melanoma by a GD2 lactone-keyhole limpet hemocyanin conjugate vaccine plus immunological adjuvant QS-21. Clin Cancer Res. 2003;9:5214–20.

    CAS  PubMed  Google Scholar 

  47. Gilewski TA, Ragupathi G, Dickler M, Powell S, Bhuta S, Panageas K, et al. Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate plus the immunologic adjuvant QS-21. Clin Cancer Res. 2007;13:2977–85.

    Article  CAS  PubMed  Google Scholar 

  48. Slovin SF, Ragupathi G, Musselli C, Olkiewicz K, Verbel D, Kuduk SD, et al. Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate cancer: clinical trial results with alpha-N-acetylgalactosamine-O-serine/threonine conjugate vaccine. J Clin Oncol. 2003;21:4292–8.

    Article  CAS  PubMed  Google Scholar 

  49. Sabbatini PJ, Ragupathi G, Hood C, Aghajanian CA, Juretzka M, Iasonos A, et al. Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer. Clin Cancer Res. 2007;13:4170–7.

    Article  CAS  PubMed  Google Scholar 

  50. Krug LM, Ragupathi G, Ng KK, Hood C, Jennings HJ, Guo Z, et al. Vaccination of small cell lung cancer patients with polysialic acid or N-propionylated polysialic acid conjugated to keyhole limpet hemocyanin. Clin Cancer Res. 2004;10:916–23.

    Article  CAS  PubMed  Google Scholar 

  51. Zanjani NT, Saksena MM, Dehghani F, Cunningham AL. From ocean to bedside: the therapeutic potential of molluscan hemocyanins. Curr Med Chem. 2018;25:2292–303.

    Article  CAS  PubMed  Google Scholar 

  52. Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat. Med. 1998;4:328–32.

    Article  CAS  PubMed  Google Scholar 

  53. De Ioannes P, Moltedo B, Oliva H, Pacheco R, Faunes F, De Ioannes AE, Becker MI. Hemocyanin of the molluscan Concholepas concholepas exhibits an unusual heterodecameric array of subunits. J Biol Chem. 2004;279:26134–42.

    Article  PubMed  Google Scholar 

  54. Villar J, Salazar ML, Jiménez JM, Campo MD, Manubens A, Gleisner MA, et al. C-type lectin receptors MR and DC-SIGN are involved in recognition of hemocyanins, shaping their immunostimulatory effects on human dendritic cells. Eur J Immunol. 2021;51:1715–31.

    Article  CAS  PubMed  Google Scholar 

  55. Reyes D, Salazar L, Espinoza E, Pereda C, Castellón E, Valdevenito R, et al. Tumor cell lysate-loaded dendritic cell vaccine induces biochemical and memory immune response in castration-resistant prostate cancer patients. Br J Cancer. 2013;109:1488–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. López MN, Pereda C, Segal G, Muñoz L, Aguilera R, González FE, et al. Prolonged survival of dendritic cell-vaccinated melanoma patients correlates with tumor-specific delayed type IV hypersensitivity response and reduction of tumor growth factor beta-expressing T cells. J Clin Oncol. 2009;27:945–52.

    Article  PubMed  Google Scholar 

  57. Leko V, Rosenberg SA. Identifying and targeting human tumor antigens for T cell-based immunotherapy of solid tumors. Cancer Cell. 2020;38:454–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Harari A, Graciotti M, Bassani-Sternberg M, Kandalaft LE. Antitumour dendritic cell vaccination in a priming and boosting approach. Nat Rev Drug Discov. 2020;19:635–52.

    Article  CAS  PubMed  Google Scholar 

  59. Blass E, Ott PA. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nat Rev Clin Oncol. 2021;18:215–29.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Klebanoff CA, Wolchok JD. Shared cancer neoantigens: making private matters public. J Exp Med. 2018;215:5–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Zhao W, Wu J, Chen S, Zhou Z. Shared neoantigens: ideal targets for off-the-shelf cancer immunotherapy. Pharmacogenomics. 2020;21:637–45.

    Article  CAS  PubMed  Google Scholar 

  62. Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, Franceschi S. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health. 2016;4:e609–16.

    Article  PubMed  Google Scholar 

  63. Wculek SK, Amores-Iniesta J, Conde-Garrosa R, Khouili SC, Melero I, Sancho D. Effective cancer immunotherapy by natural mouse conventional type-1 dendritic cells bearing dead tumor antigen. J Immunother Cancer. 2019;7:100.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Stone JD, Harris DT, Kranz DM. TCR affinity for p/MHC formed by tumor antigens that are self-proteins: impact on efficacy and toxicity. Curr Opin Immunol. 2015;33:16–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Nüssing S, Trapani JA, Parish IA. Revisiting T cell tolerance as a checkpoint target for cancer immunotherapy. Front Immunol. 2020;11:589641.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Hollingsworth RE, Jansen K. Turning the corner on therapeutic cancer vaccines. NPJ Vaccines. 2019;4:7.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Kravtsov DS, Erbe AK, Sondel PM, Rakhmilevich AL. Roles of CD4+ T cells as mediators of antitumor immunity. Front Immunol. 2022;13:972021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Barbieri I, Kouzarides T. Role of RNA modifications in cancer. Nat Rev Cancer. 2020;20:303–22.

    Article  CAS  PubMed  Google Scholar 

  69. Amweg A, Tusup M, Cheng P, Picardi E, Dummer R, Levesque MP, et al. The A to I editing landscape in melanoma and its relation to clinical outcome. RNA Biol. 2022;19:996–1006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Gulley JL, Madan RA, Pachynski R, Mulders P, Sheikh NA, Trager J, et al. Role of antigen spread and distinctive characteristics of immunotherapy in cancer treatment. J Natl Cancer Inst. 2017;109:djw261.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Kroemer G, Galassi C, Zitvogel L, Galluzzi L. Immunogenic cell stress and death. Nat Immunol. 2022;23:487–500.

    Article  CAS  PubMed  Google Scholar 

  72. Gallucci S, Lolkema M, Matzinger P. Natural adjuvants: endogenous activators of dendritic cells. Nat Med. 1999;5:1249–55.

    Article  CAS  PubMed  Google Scholar 

  73. Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med. 2000;191:423–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13:54–61.

    Article  CAS  PubMed  Google Scholar 

  75. Harris H, Andersson U, Pisetsky D. HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol. 2012;8:195–202.

    Article  CAS  PubMed  Google Scholar 

  76. Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2017;13:1050–9.

    Article  Google Scholar 

  77. Bedoui S, Herold MJ, Strasser A. Emerging connectivity of programmed cell death pathways and its physiological implications. Nat Rev Mol Cell Biol. 2020;21:678–95.

    Article  CAS  PubMed  Google Scholar 

  78. Schiavoni G, Sistigu A, Valentini M, Mattei F, Sestili P, Spadaro F, et al. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res. 2011;71:768–78.

    Article  CAS  PubMed  Google Scholar 

  79. Golden EB, Apetoh L. Radiotherapy and immunogenic cell death. Semin Radiat Oncol. 2015;25:11–7.

    Article  PubMed  Google Scholar 

  80. Alzeibak R, Mishchenko TA, Shilyagina NY, Balalaeva IV, Vedunova MV, Krysko DV. Targeting immunogenic cancer cell death by photodynamic therapy: past, present and future. J Immunother Cancer. 2021;9:e001926.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Fucikova J, Moserova I, Truxova I, Hermanova I, Vancurova I, Partlova S, et al. High hydrostatic pressure induces immunogenic cell death in human tumor cells. Int J Cancer. 2014;135:1165–77.

    Article  CAS  PubMed  Google Scholar 

  82. Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 2012;12:860–75.

    Article  CAS  PubMed  Google Scholar 

  83. Podolska MJ, Shan X, Janko C, Boukherroub R, Gaipl US, Szunerits S, et al. Graphene-induced hyperthermia (GIHT) combined with radiotherapy fosters immunogenic cell death. Front Oncol. 2021;11:664615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Minute L, Teijeira A, Sanchez-Paulete AR, Ochoa MC, Alvarez M, Otano I, et al. Cellular cytotoxicity is a form of immunogenic cell death. J Immunother Cancer. 2020;8:e000325.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Jaime-Sanchez P, Uranga-Murillo I, Aguilo N, Khouili SC, Arias MA, Sancho D, et al. Cell death induced by cytotoxic CD8+ T cells is immunogenic and primes caspase-3-dependent spread immunity against endogenous tumor antigens. J Immunother Cancer. 2020;8:e000528.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Yatim N, Jusforgues-Saklani H, Orozco S, Schulz O, Barreira da Silva R, Reis e Sousa C, et al. RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8+ T cells. Science. 2015;350:328–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Aaes TL, Kaczmarek A, Delvaeye T, De Craene B, De Koker S, Heyndrickx L, et al. Vaccination with necroptotic cancer cells induces efficient antitumor immunity. Cell Rep. 2016;15:274–87.

    Article  CAS  PubMed  Google Scholar 

  88. Snyder AG, Hubbard NW, Messmer MN, Kofman SB, Hagan CE, Orozco SL, et al. Intratumoral activation of the necroptotic pathway components RIPK1 and RIPK3 potentiates antitumor immunity. Sci Immunol. 2019;4:eaaw2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Sprooten J, De Wijngaert P, Vanmeerbeerk I, Martin S, Vangheluwe P, Schlenner S, et al. Necroptosis in immuno-oncology and cancer immunotherapy. Cells. 2020;9:1823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Wang Y, Gao W, Shi X, Ding J, Liu W, He H, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a mastermind. Nature. 2017;547:99–103.

    Article  CAS  PubMed  Google Scholar 

  91. Hou J, Zhao R, Xia W, Chang CW, You Y, Hsu JM, et al. PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumor necrosis. Nat Cell Biol. 2020;22:1264–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Zhou Z, He H, Wang K, Shi X, Wang Y, Su Y, et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science. 2020;368:eaaz7548.

    Article  CAS  PubMed  Google Scholar 

  93. Wang W, Green M, Choi JE, Gijón M, Kennedy PD, Johnson JK, et al. CD8+ T cells regulate tumor ferroptosis during cancer immunotherapy. Nature. 2019;569:270–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Efimova I, Catanzaro E, Van der Meeren L, Turubanova VD, Hammad H, Mishchenko TA, et al. Vaccination with early ferroptotic cancer cells induces efficient antitumor immunity. J Immunother Cancer. 2020;8:e001369.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Tang D, Kepp O, Kroemer G. Ferroptosis becomes immunogenic: implications for anticancer treatments. Oncoimmunology. 2020;10:1862949.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Wiernicki B, Maschalidi S, Pinney J, Adjemian S, Vanden Berghe T, Ravichandran KS, et al. Cancer cells dying from ferroptosis impede dendritic cell-mediated antitumor immunity. Nat Commun. 2022;13:3676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Aguilera R, Saffie C, Tittarelli A, González FE, Ramírez M, Reyes D, et al. Heat-shock induction of tumor-derived danger signals mediates rapid monocyte differentiation into clinically effective dendritic cells. Clin Cancer Res. 2011;17:2474–83.

    Article  CAS  PubMed  Google Scholar 

  98. Rojas-Sepúlveda D, Tittarelli A, Gleisner MA, Ávalos I, Pereda C, Gallegos I, et al. Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer. Cancer Immunol Immunother. 2018;67:1897–910.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Flores I, Hevia D, Tittarelli A, Soto D, Rojas-Sepúlveda D, Pereda C, et al. Dendritic cells loaded with heat shock-conditioned ovarian epithelial carcinoma cell lysates elicit T cell-dependent antitumor immune responses in vitro. J Immunol Res. 2019;2019:9631515.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Gleisner MA, Pereda C, Tittarelli A, Navarrete M, Fuentes C, Ávalos I, et al. A heat-shocked melanoma cell lysate vaccine enhances tumor infiltration by prototypic effector T cells inhibiting tumor growth. J Immunother Cancer. 2020;8:e000999.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Chiang CL, Kandalaft LE, Tanyi J, Hagemann AR, Motz GT, Svoronos N, et al. A dendritic cell vaccine pulsed with autologous hypochlorous acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside. Clin Cancer Res. 2013;19:4801–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Zhou R, Huang WJ, Ma C, Zhou Y, Yao YQ, Wang YX, et al. HOCl oxidation-modified CT26 cell vaccine inhibits colon tumor growth in a mouse model. Asian Pac J Cancer Prev. 2012;13:4037–43.

    Article  PubMed  Google Scholar 

  103. Maes H, Rubio N, Garg AD, Agostinis P. Autophagy: shaping the tumor microenvironment and therapeutic response. Trends Mol Med. 2013;19:428–46.

    Article  CAS  PubMed  Google Scholar 

  104. Li Y, Wang LX, Pang P, Twitty C, Fox BA, Aung S, et al. Cross-presentation of tumor-associated antigens through tumor-derived autophagosomes. Autophagy. 2009;5:576–7.

    Article  CAS  PubMed  Google Scholar 

  105. Princiotta MF, Finzi D, Qian SB, Gibbs J, Schuchmann S, Buttgereit F, et al. Quantitating protein synthesis, degradation, and endogenous antigen processing. Immunity. 2003;18:343–54.

    Article  CAS  PubMed  Google Scholar 

  106. Xing Y, Cao R, Hu HM. TLR and NLRP3 inflammasome-dependent innate immune responses to tumor-derived autophagosomes (DRibbles). Cell Death Dis. 2016;7:e2322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Li Y, Wang LX, Pang P, Cui Z, Aung S, Haley D, et al. Tumor-derived autophagosome vaccine: mechanism of cross-presentation and therapeutic efficacy. Clin Cancer Res. 2011;17:7047–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. McRae BL, Vanderlugt CL, Dal Canto MC, Miller SD. Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis. J Exp Med. 1995;182:75–85.

    Article  CAS  PubMed  Google Scholar 

  109. Ribas A, Timmerman JM, Butterfield LH, Economou JS. Determinant spreading and tumor responses after peptide-based cancer immunotherapy. Trends Immunol. 2003;24:58–61.

    Article  CAS  PubMed  Google Scholar 

  110. Menares E, Gálvez-Cancino F, Cáceres-Morgado P, Ghorani E, López E, Díaz X, et al. Tissue-resident memory CD8+ T cells amplify antitumor immunity by triggering antigen spreading through dendritic cells. Nat Commun. 2019;10:4401.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Brossart P. The role of antigen spreading in the efficacy of immunotherapies. Clin Cancer Res. 2020;26:4442–7.

    Article  CAS  PubMed  Google Scholar 

  112. Kvedaraite E, Ginhoux F. Human dendritic cells in cancer. Sci Immunol. 2022;7:eabm9409.

    Article  CAS  PubMed  Google Scholar 

  113. Joffre OP, Segura E, Savina A, Amigorena S. Cross-presentation by dendritic cells. Nat Rev Immunol. 2012;12:557–69.

    Article  CAS  PubMed  Google Scholar 

  114. Böttcher JP, Reis e Sousa C. The role of type 1 conventional dendritic cells in cancer immunity. Trends Cancer. 2018;4:784–92.

    Article  PubMed  PubMed Central  Google Scholar 

  115. MacNabb BW, Tumuluru S, Chen X, Godfrey J, Kasal DN, Yu J, et al. Dendritic cells can prime antitumor CD8+ T cell responses through major histocompatibility complex cross-dressing. Immunity. 2022;55:982.e8–97.e8.

    Article  Google Scholar 

  116. Enamorado M, Iborra S, Priego E, Cueto FJ, Quintana JA, Martínez-Cano S, et al. Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8+ T cells. Nat Commun. 2017;8:16073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Hoch T, Schulz D, Eling N, Gómez JM, Levesque MP, Bodenmiller B. Multiplexed imaging mass cytometry of the chemokine milieus in melanoma characterizes features of the response to immunotherapy. Sci Immunol. 2022;7:eabk1692.

    Article  CAS  PubMed  Google Scholar 

  118. Garris CS, Arlauckas SP, Kohler RH, Trefny MP, Garren S, Piot C, et al. Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12. Immunity. 2018;49:1148.e7–61.e7.

    Article  Google Scholar 

  119. Balan S, Radford KJ, Bhardwaj N. Unexplored horizons of cDC1 in immunity and tolerance. Adv Immunol. 2020;148:49–91.

    Article  CAS  PubMed  Google Scholar 

  120. Tel J, Aarntzen EH, Baba T, Schreibelt G, Schulte BM, Benitez-Ribas D, et al. Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients. Cancer Res. 2013;73:1063–75.

    Article  CAS  PubMed  Google Scholar 

  121. Binnewies M, Mujal AM, Pollack JL, Combes AJ, Hardison EA, Barry KC, et al. Unleashing type-2 dendritic cells to drive protective antitumor CD4+ T cell immunity. Cell. 2019;177:556.e16–71.e16.

    Article  Google Scholar 

  122. Aspord C, Leccia MT, Charles J, Plumas J. Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL. Cancer Immunol Res. 2013;1:402–15.

    Article  CAS  PubMed  Google Scholar 

  123. Guilliams M, Crozat K, Henri S, Tamoutounour S, Grenot P, Devilard E, et al. Skin-draining lymph nodes contain dermis-derived CD103(−) dendritic cells that constitutively produce retinoic acid and induce Foxp3(+) regulatory T cells. Blood. 2010;115:1958–68.

    Article  CAS  PubMed  Google Scholar 

  124. Segura E, Touzot M, Bohineust A, Cappuccio A, Chiocchia G, Hosmalin A, et al. Human inflammatory dendritic cells induce Th17 cell differentiation. Immunity. 2013;38:336–48.

    Article  CAS  PubMed  Google Scholar 

  125. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.

    Article  CAS  PubMed  Google Scholar 

  126. Liau LM, Ashkan K, Brem S, Campian JL, Trusheim JE, Iwamoto FM, et al. Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: a phase 3 prospective externally controlled cohort trial. JAMA Oncol. 2023;9:112–21.

    Article  PubMed  Google Scholar 

  127. González FE, Gleisner A, Falcón-Beas F, Osorio F, López MN, Salazar-Onfray F. Tumor cell lysates as immunogenic sources for cancer vaccine design. Hum Vaccin Immunother. 2014;10:3261–9.

    Article  PubMed  Google Scholar 

  128. Shi H, Cao T, Connolly JE, Monnet L, Bennett L, Chapel S, et al. Hyperthermia enhances CTL cross-priming. J Immunol. 2006;176:2134–41.

    Article  CAS  PubMed  Google Scholar 

  129. Frank MJ, Khodadoust MS, Czerwinski DK, Haabeth OAW, Chu MP, Miklos DB, et al. Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: a phase I/II trial. J Exp Med. 2020;217:e20191712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Dörrie J, Schaft N, Schuler G, Schuler-Thurner B. Therapeutic cancer vaccination with ex vivo RNA-transfected dendritic cells-an update. Pharmaceutics. 2020;12:92.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Bol KF, Schreiber G, Rabold K, Wculek SK, Schwarze JK, Dzionek A, et al. The clinical application of cancer immunotherapy based on naturally circulating dendritic cells. J Immunother Cancer. 2019;7:109.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Lei X, Lei Y, Li JK, Du WX, Li RG, Yang J, et al. Immune cells within the tumor microenvironment: biological functions and roles in cancer immunotherapy. Cancer Lett. 2020;470:126–33.

    Article  CAS  PubMed  Google Scholar 

  133. Dai E, Zhu Z, Wahid S, Qu Z, Storkus WJ, Guo ZS. Epigenetic modulation of antitumor immunity for improved cancer immunotherapy. Mol Cancer. 2021;20:171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Watson MJ, Vignali PDA, Mullett SJ, Overacre-Delgoffe AE, Peralta RM, Grebinoski S, et al. Metabolic support of tumor-infiltrating regulatory T cells by lactic acid. Nature. 2021;591:645–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T-cell immunity. Cancer Cell. 2014;26:638–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Spranger S, Dai D, Horton B, Gajewski TF. Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell. 2017;31:711.e4–23.e4.

    Article  Google Scholar 

  137. Verneau J, Sautés-Fridman C, Sun CM. Dendritic cells in the tumor microenvironment: prognostic and theranostic impact. Semin Immunol. 2020;48:101410.

    Article  CAS  PubMed  Google Scholar 

  138. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20:5064–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321–30.

    Article  CAS  PubMed  Google Scholar 

  140. Tarhini AA, Edington H, Butterfield LH, Lin Y, Shuai Y, Tawbi H, et al. Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab. PLoS ONE. 2014;9:e87705.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Berry J, Vreeland T, Trappey A, Hale D, Peace K, Tyler J, et al. Cancer vaccines in colon and rectal cancer over the last decade: lessons learned and future directions. Expert Rev Clin Immunol. 2017;13:235–45.

    Article  CAS  PubMed  Google Scholar 

  142. Naimi A, Mohammed RN, Raji A, Chupradit S, Yumashev AV, Suksatan W, et al. Tumor immunotherapies by immune checkpoint inhibitors (ICIs), the pros and cons. Cell Commun Signal. 2022;20:44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Apetoh L, Smyth MJ, Drake CG, Abastado JP, Apte RN, Ayyoub M, et al. Consensus nomenclature for CD8+ T cell phenotypes in cancer. Oncoimmunology. 2015;4:e998538.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12:492–9.

    Article  CAS  PubMed  Google Scholar 

  145. Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol. 2003;77:4911–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2009;10:29–37.

    Article  CAS  PubMed  Google Scholar 

  147. Jin HT, Anderson AC, Tan WG, West EE, Ha SJ, Araki K, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci USA. 2010;107:14733–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Fourcade J, Sun Z, Pagliano O, Guillaume P, Luescher IF, Sander C, et al. CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1. Cancer Res. 2012;72:887–96.

    Article  CAS  PubMed  Google Scholar 

  149. Joller N, Hafler JP, Brynedal B, Kassam N, Spoerl S, Levin SD, et al. Cutting edge: TIGIT has T cell-intrinsic inhibitory functions. J Immunol. 2011;186:1338–42.

    Article  CAS  PubMed  Google Scholar 

  150. Kansy BA, Concha-Benavente F, Srivastava RM, Jie HB, Shayan G, Lei Y, et al. PD-1 status in CD8+ T cells associates with survival and anti-PD-1 therapeutic outcomes in head and neck cancer. Cancer Res. 2017;77:6353–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Arce Vargas F, Furness AJS, Solomon I, Joshi K, Mekkaoui L, Lesko MH, et al. Fc-optimized anti-CD25 depletes tumor-infiltrating regulatory T cells and synergizes with PD-1 blockade to eradicate established tumors. Immunity. 2017;46:577–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Aijaz A, Li M, Smith D, Khong D, LeBlon C, Fenton OS, et al. Biomanufacturing for clinically advanced cell therapies. Nat Biomed Eng. 2018;2:362–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Jian Y, Yang K, Sun X, Zhao J, Huang K, Aldanakh A, et al. Current advance of immune evasion mechanisms and emerging immunotherapies in renal cell carcinoma. Front Immunol. 2021;12:639636.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Ribas A, Hodi FS, Callahan M, Konto C, Wolchok J. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med. 2013;368:1365–6.

    Article  CAS  PubMed  Google Scholar 

  155. Adkins I, Sadilkova L, Hradilova N, Tomala J, Kovar M, Spisek R. Severe, but not mild heat-shock treatment induces immunogenic cell death in cancer cells. Oncoimmunology. 2017;6:e1311433.

    Article  PubMed  PubMed Central  Google Scholar 

  156. Turubanova VD, Mishchenko TA, Balalaeva IV, Efimova I, Peskova NN, Klapshina LG, et al. Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death. Sci Rep. 2021;11:7205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Vuky J, Corman JM, Porter C, Olgac S, Auerbach E, Dahl K. Phase II trial of neoadjuvant docetaxel and CG1940/CG8711 followed by radical prostatectomy in patients with high-risk clinically localized prostate cancer. Oncologist. 2013;18:687–8.

    Article  PubMed  PubMed Central  Google Scholar 

  158. Michael BD, Syndikus I, Clark A, Baborie A. Diffuse primary leptomeningeal melanocytosis in a patient receiving a novel cancer cell vaccine for prostate cancer. BMJ Case Rep. 2010;2010:bcr11.2009.2495.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Hardacre JM, Mulcahy M, Small W, Talamonti M, Obel J, Krishnamurthi S, et al. Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer: a phase 2 study. J Gastrointest Surg. 2013;17:94–101.

    Article  PubMed  Google Scholar 

  160. Hewitt DB, Nissen N, Hatoum H, Musher B, Seng J, Coveler AL, et al. A phase 3 randomized clinical trial of chemotherapy with or without algenpantucel-L (hyperacute-pancreas) immunotherapy in subjects with borderline resectable or locally advanced unresectable pancreatic cancer. Ann Surg. 2022;275:45–53.

    Article  PubMed  Google Scholar 

  161. Barve V, Adams N, Stanbery L, Manning L, Horvath S, Wallraven G, et al. Case report: marked survival advantage of two colorectal cancer patients with liver metastases treated with vigil and FOLFOX-6. Vaccines. 2021;9:1201.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M, et al. Phase I trial of “bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell” vaccine (FANG) in advanced cancer. Mol Ther. 2012;20:679–86.

    Article  CAS  PubMed  Google Scholar 

  163. Wiseman CL, Kharazi A, Sunkari VG, Galeas JL, Dozio V, Hashwah H, et al. Regression of breast cancer metastases following treatment with irradiated SV-BR-1-GM, a GM-CSF overexpressing breast cancer cell line: intellectual property and immune markers of response. Recent Pat Anticancer Drug Discov. 2022;18:224–40.

    PubMed  Google Scholar 

  164. Aris M, Bravo AI, Pampena MB, Blanco PA, Carri I, Koile D, et al. Changes in the TCRβ repertoire and tumor immune signature from a cutaneous melanoma patient immunized with the CSF-470 vaccine: a case report. Front Immunol. 2018;9:955.

    Article  PubMed  PubMed Central  Google Scholar 

  165. Schuler-Thurner B, Bartz-Schmidt KU, Bornfeld N, Cursiefen C, Fuisting B, Grisanti S, et al. Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma. Ophthalmologe. 2015;112:1017–21.

    Article  CAS  PubMed  Google Scholar 

  166. Vik-Mo EO, Nyakas M, Mikkelsen BV, Moe MC, Due-Tønnesen P, Suso EM, et al. Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma. Cancer Immunol Immunother. 2013;62:1499–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Chang CN, Huang YC, Yang DM, Kikuta K, Wei KJ, Kubota T, et al. A phase I/II clinical trial investigating the adverse and therapeutic effects of a postoperative autologous dendritic cell tumor vaccine in patients with malignant glioma. J Clin Neurosci. 2011;18:1048–54.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Marisol Briones (Universidad de Chile) for the administrative and technical support.

Author information

Author notes

  1. These authors contributed equally: Amarilis Pérez-Baños, María Alejandra Gleisner.

Authors and Affiliations

  1. Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile

    Amarilis Pérez-Baños, María Alejandra Gleisner, Iván Flores, Cristián Pereda, Mariela Navarrete, Juan Pablo Araya & Flavio Salazar-Onfray

  2. Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, Universidad de Chile, Santiago, Chile

    Amarilis Pérez-Baños, María Alejandra Gleisner, Iván Flores, Cristián Pereda, Mariela Navarrete, Juan Pablo Araya, Giovanna Navarro, Claudia Quezada-Monrás & Flavio Salazar-Onfray

  3. Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, 5110566, Chile

    Giovanna Navarro & Claudia Quezada-Monrás

  4. Programa Institucional de Fomento a la Investigación, Desarrollo e Innovación (PIDi), Universidad Tecnológica Metropolitana (UTEM), Santiago, Chile

    Andrés Tittarelli

  5. Science for Life Laboratory, Department of Medicine Solna, Karolinska Institute and Section for Infectious Diseases, Karolinska University Hospital, 17176, Stockholm, Sweden

    Flavio Salazar-Onfray

Authors
  1. Amarilis Pérez-Baños
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. María Alejandra Gleisner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Iván Flores
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cristián Pereda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mariela Navarrete
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Juan Pablo Araya
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giovanna Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Claudia Quezada-Monrás
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrés Tittarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Flavio Salazar-Onfray
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Literature search and chapter writing (AP-B, MAG, IF, CP), critical review and corrections (MN, JPA, GN, CQ), figures, conceptualisation, and manuscript writing (AT, FS-O).

Corresponding authors

Correspondence to Andrés Tittarelli or Flavio Salazar-Onfray.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pérez-Baños, A., Gleisner, M.A., Flores, I. et al. Whole tumour cell-based vaccines: tuning the instruments to orchestrate an optimal antitumour immune response. Br J Cancer 129, 572–585 (2023). https://doi.org/10.1038/s41416-023-02327-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-023-02327-6

This article is cited by

Search

Advanced search

Quick links