Attard, G. et al. Prostate cancer. Lancet 387, 70–82 (2016).
McNeel, D. G. et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma. J. Immunother. Cancer. 4, 92 (2016).
Maia, M. C. & Hansen, A. R. A comprehensive review of immunotherapies in prostate cancer. Crit. Rev. Oncol. Hematol. 113, 292–303 (2017).
Karan, D., Holzbeierlein, J. M., Van Veldhuizen, P. & Thrasher, J. B. Cancer immunotherapy: a paradigm shift for prostate cancer treatment. Nat. Rev. Urol. 9, 376–385 (2012).
Yap, T. A. et al. Drug discovery in advanced prostate cancer: translating biology into therapy. Nat. Rev. Drug Discov. 15, 699–718 (2016).
Topalian, S. L., Drake, C. G. & Pardoll, D. M. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer. Cell. 27, 450–461 (2015).
Drake, C. G. Prostate cancer as a model for tumour immunotherapy. Nat. Rev. Immunol. 10, 580–593 (2010).
Kiessling, A. et al. Advances in specific immunotherapy for prostate cancer. Eur. Urol. 53, 694–708 (2008).
Silvestri, I. et al. A perspective of immunotherapy for prostate cancer. Cancers 8, E64 (2016).
Di Lorenzo, G., Buonerba, C. & Kantoff, P. W. Immunotherapy for the treatment of prostate cancer. Nat. Rev. Clin. Oncol. 8, 551–561 (2011).
Lichty, B. D., Breitbach, C. J., Stojdl, D. F. & Bell, J. C. Going viral with cancer immunotherapy. Nat. Rev. Cancer. 14, 559–567 (2014).
Taguchi, S., Fukuhara, H., Homma, Y. & Todo, T. Current status of clinical trials assessing oncolytic virus therapy for urological cancers. Int. J. Urol. 24, 342–351 (2017).
Gujar, S., Pol, J. G., Kim, Y., Lee, P. W. & Kroemer, G. Antitumor benefits of antiviral immunity: an underappreciated aspect of oncolytic virotherapies. Trends Immunol. https://doi.org/10.1016/j.it.2017.11.006 (2017).
Delwar, Z., Zhang, K., Rennie, P. S. & Jia, W. Oncolytic virotherapy for urological cancers. Nat. Rev. Urol. 13, 334–352 (2016).
Gravitz, L. Cancer immunotherapy. Nature 504, S1 (2013).
Sharma, P. & Allison, J. P. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell 161, 205–214 (2015).
Peshwa, M. V., Shi, J. D., Ruegg, C., Laus, R. & van Schooten, W. C. Induction of prostate tumor-specific CD8+ cytotoxic T-lymphocytes in vitro using antigen-presenting cells pulsed with prostatic acid phosphatase peptide. Prostate 36, 129–138 (1998).
Machlenkin, A. et al. Human CTL epitopes prostatic acid phosphatase-3 and six-transmembrane epithelial antigen of prostate-3 as candidates for prostate cancer immunotherapy. Cancer Res. 65, 6435–6442 (2005).
Johnson, L. E., Frye, T. P., Chinnasamy, N., Chinnasamy, D. & McNeel, D. G. Plasmid DNA vaccine encoding prostatic acid phosphatase is effective in eliciting autologous antigen-specific CD8+ T cells. Cancer Immunol. Immunother. 56, 885–895 (2007).
Gujar, S. A., Pan, D. A., Marcato, P., Garant, K. A. & Lee, P. W. Oncolytic virus-initiated protective immunity against prostate cancer. Mol. Ther. 19, 797–804 (2011).
Pitt, J. M. et al. Resistance mechanisms to immune-checkpoint blockade in cancer: tumor-intrinsic and -extrinsic factors. Immunity 44, 1255–1269 (2016).
Barach, Y. S., Lee, J. S. & Zang, X. T cell coinhibition in prostate cancer: new immune evasion pathways and emerging therapeutics. Trends Mol. Med. 17, 47–55 (2011).
Vesely, M. D. & Schreiber, R. D. Cancer immunoediting: antigens, mechanisms, and implications to cancer immunotherapy. Ann. NY Acad. Sci. 1284, 1–5 (2013).
Ostrand-Rosenberg, S., Sinha, P., Beury, D. W. & Clements, V. K. Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin. Cancer Biol. 22, 275–281 (2012).
Gajewski, T. F., Schreiber, H. & Fu, Y. X. Innate and adaptive immune cells in the tumor microenvironment. Nat. Immunol. 14, 1014–1022 (2013).
van der Burg, S. H., Arens, R., Ossendorp, F., van Hall, T. & Melief, C. J. Vaccines for established cancer: overcoming the challenges posed by immune evasion. Nat. Rev. Cancer. 16, 219–233 (2016).
Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).
Smyth, M. J., Ngiow, S. F., Ribas, A. & Teng, M. W. Combination cancer immunotherapies tailored to the tumour microenvironment. Nat. Rev. Clin. Oncol. 13, 143–158 (2016).
Modena, A. et al. Immune checkpoint inhibitors and prostate cancer: a new frontier? Oncol. Rev. 10, 293 (2016).
Gujar, S. et al. Multifaceted therapeutic targeting of ovarian peritoneal carcinomatosis through virus-induced immunomodulation. Mol. Ther. 21, 338–347 (2013).
Gujar, S. A., Marcato, P., Pan, D. & Lee, P. W. Reovirus virotherapy overrides tumor antigen presentation evasion and promotes protective antitumor immunity. Mol. Cancer. Ther. 9, 2924–2933 (2010).
Zhao, X., Chester, C., Rajasekaran, N., He, Z. & Kohrt, H. E. Strategic combinations: the future of oncolytic virotherapy with reovirus. Mol. Cancer. Ther. 15, 767–773 (2016).
Fend, L. et al. Immune checkpoint blockade, immunogenic chemotherapy or IFN-alpha blockade boost the local and abscopal effects of oncolytic virotherapy. Cancer Res. 77, 4146–4157 (2017).
Tanoue, K. et al. Armed oncolytic adenovirus-expressing PD-L1 mini-body enhances antitumor effects of chimeric antigen receptor T cells in solid tumors. Cancer Res. 77, 2040–2051 (2017).
Montironi, R. et al. Emerging immunotargets and immunotherapies in prostate cancer. Curr. Drug Targets 17, 777–782 (2016).
Lu, X. et al. Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature 543, 728–732 (2017).
Gao, J. et al. VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat. Med. 23, 551–555 (2017).
Zitvogel, L., Apetoh, L., Ghiringhelli, F. & Kroemer, G. Immunological aspects of cancer chemotherapy. Nat. Rev. Immunol. 8, 59–73 (2008).
Chen, D. S. & Mellman, I. Elements of cancer immunity and the cancer-immune set point. Nature 541, 321–330 (2017).
Jung, S. et al. In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity 17, 211–220 (2002).
Baas, W. et al. Immune characterization of the programmed death receptor pathway in high risk prostate cancer. Clin. Genitourin. Cancer 15, 577–581 (2017).
Madan, R. A. & Gulley, J. L. Prostate cancer: Better VISTAs ahead? Potential and pitfalls of immunotherapy. Nat. Rev. Urol. 14, 455–456 (2017).
Sfanos, K. S. et al. Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+. Prostate 69, 1694–1703 (2009).
De Marzo, A. M. et al. Inflammation in prostate carcinogenesis. Nat. Rev. Cancer 7, 256–269 (2007).
Taylor, B. S. et al. Integrative genomic profiling of human prostate cancer. Cancer. Cell. 18, 11–22 (2010).
Tan, S. H. et al. Evaluation of ERG responsive proteome in prostate cancer. Prostate 74, 70–89 (2014).
Kim, J. J. et al. Induction of immune responses and safety profiles in rhesus macaques immunized with a DNA vaccine expressing human prostate specific antigen. Oncogene 20, 4497–4506 (2001).
Sfanos, K. S. et al. Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin. Cancer Res. 14, 3254–3261 (2008).
Lopez-Bujanda, Z. & Drake, C. G. Myeloid-derived cells in prostate cancer progression: phenotype and prospective therapies. J. Leukoc. Biol. 102, 393–406 (2017).
Sizemore, G. M. et al. Stromal PTEN inhibits the expansion of mammary epithelial stem cells through Jagged-1. Oncogene 36, 2297–2308 (2017).
Kaukonen, R. et al. Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription. Nat. Commun. 7, 12237 (2016).
Turley, S. J., Cremasco, V. & Astarita, J. L. Immunological hallmarks of stromal cells in the tumour microenvironment. Nat. Rev. Immunol. 15, 669–682 (2015).
Kalluri, R. The biology and function of fibroblasts in cancer. Nat. Rev. Cancer. 16, 582–598 (2016).
Nagarsheth, N., Wicha, M. S. & Zou, W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat. Rev. Immunol. 17, 559–572 (2017).
Vinay, D. S. et al. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin. Cancer Biol. 35 (Suppl.), S185–S198 (2015).
Carmeliet, P. & Jain, R. K. Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298–307 (2011).
Smith, B. A. et al. A basal stem cell signature identifies aggressive prostate cancer phenotypes. Proc. Natl Acad. Sci. USA 112, E6544–E6552 (2015).
Chauhan, A. & Anthony, L. Immune oncology and neuroendocrine tumors. Ann. Oncol. 28, 2322–2323 (2017).
Alvarado, A. G. et al. Glioblastoma cancer stem cells evade innate immune suppression of self-renewal through reduced TLR4 expression. Cell. Stem Cell. 20, 450–461.e4 (2017).
Sultan, M. et al. Hide-and-seek: the interplay between cancer stem cells and the immune system. Carcinogenesis 38, 107–118 (2017).
Bishop, J., Sangha, B., Gleave, M. & Zoubeidi, A. Immune evasion strategies of neuroendocrine-like Enzalutamide resistant prostate cancer. J. Immunother. Cancer 1 (Suppl. 1), P147 (2013).
Bronte, V. et al. Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers. J. Exp. Med. 201, 1257–1268 (2005).
Mercader, M. et al. T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer. Proc. Natl Acad. Sci. USA 98, 14565–14570 (2001).
Healy, C. G. et al. Impaired expression and function of signal-transducing zeta chains in peripheral T cells and natural killer cells in patients with prostate cancer. Cytometry 32, 109–119 (1998).
Ness, N. et al. The prognostic role of immune checkpoint markers programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) in a large, multicenter prostate cancer cohort. Oncotarget 8, 26789–26801 (2017).
Morse, M. D. & McNeel, D. G. T cells localized to the androgen-deprived prostate are TH1 and TH17 biased. Prostate 72, 1239–1247 (2012).
Zhang, Q. et al. Targeting Th17-IL-17 pathway in prevention of micro-invasive prostate cancer in a mouse model. Prostate 77, 888–899 (2017).
Foster, B. A., Gingrich, J. R., Kwon, E. D., Madias, C. & Greenberg, N. M. Characterization of prostatic epithelial cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Cancer Res. 57, 3325–3330 (1997).
Hurwitz, A. A., Foster, B. A., Allison, J. P., Greenberg, N. M. & Kwon, E. D. in Current Protocols in Immunology (eds Coligan, J. E. et al.) Unit 20.5 (2001).
Won, H. et al. TLR9 expression and secretion of LIF by prostate cancer cells stimulates accumulation and activity of polymorphonuclear MDSCs. J. Leukoc. Biol. 102, 423–436 (2017).
Leventhal, D. S. et al. Dendritic cells coordinate the development and homeostasis of organ-specific regulatory T cells. Immunity 44, 847–859 (2016).
Pasero, C. et al. Inherent and tumor-driven immune tolerance in the prostate microenvironment impairs natural killer cell antitumor activity. Cancer Res. 76, 2153–2165 (2016).
Ammirante, M., Luo, J. L., Grivennikov, S., Nedospasov, S. & Karin, M. B-Cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature 464, 302–305 (2010).
Shalapour, S. et al. Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy. Nature 521, 94–98 (2015).
Kwek, S. S., Cha, E. & Fong, L. Unmasking the immune recognition of prostate cancer with CTLA4 blockade. Nat. Rev. Cancer. 12, 289–297 (2012).
Goswami, S., Aparicio, A. & Subudhi, S. K. Immune checkpoint therapies in prostate cancer. Cancer J. 22, 117–120 (2016).
Kambayashi, T. & Laufer, T. M. Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell? Nat. Rev. Immunol. 14, 719–730 (2014).
Gujar, S. A. & Lee, P. W. Oncolytic virus-mediated reversal of impaired tumor antigen presentation. Front. Oncol. 4, 77 (2014).
Wennier, S. T., Liu, J. & McFadden, G. Bugs and drugs: oncolytic virotherapy in combination with chemotherapy. Curr. Pharm. Biotechnol. 13, 1817–1833 (2012).
Marcato, P., Shmulevitz, M., Pan, D., Stoltz, D. & Lee, P. W. Ras transformation mediates reovirus oncolysis by enhancing virus uncoating, particle infectivity, and apoptosis-dependent release. Mol. Ther. 15, 1522–1530 (2007).
Russell, S. J. & Peng, K. W. Oncolytic virotherapy: a contest between apples and oranges. Mol. Ther. 25, 1107–1116 (2017).
Bell, J. & McFadden, G. Viruses for tumor therapy. Cell. Host Microbe 15, 260–265 (2014).
Parato, K. A., Lichty, B. D. & Bell, J. C. Diplomatic immunity: turning a foe into an ally. Curr. Opin. Mol. Ther. 11, 13–21 (2009).
Shmulevitz, M., Marcato, P. & Lee, P. W. Unshackling the links between reovirus oncolysis, Ras signaling, translational control and cancer. Oncogene 24, 7720–7728 (2005).
Strong, J. E., Coffey, M. C., Tang, D., Sabinin, P. & Lee, P. W. The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. EMBO J. 17, 3351–3362 (1998).
Coffey, M. C., Strong, J. E., Forsyth, P. A. & Lee, P. W. Reovirus therapy of tumors with activated Ras pathway. Science 282, 1332–1334 (1998).
Kirn, D. Replication-selective oncolytic adenoviruses: virotherapy aimed at genetic targets in cancer. Oncogene 19, 6660–6669 (2000).
Andtbacka, R. H. et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J. Clin. Oncol. 33, 2780–2788 (2015).
Rehman, H., Silk, A. W., Kane, M. P. & Kaufman, H. L. Into the clinic: Talimogene laherparepvec (T-VEC), a first-in-class intratumoral oncolytic viral therapy. J. Immunother. Cancer. 4, 53 (2016).
Schvartsman, G., Perez, K., Flynn, J. E., Myers, J. N. & Tawbi, H. Safe and effective administration of T-VEC in a patient with heart transplantation and recurrent locally advanced melanoma. J. Immunother. Cancer. 5, 45 (2017).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00769704 (2016).
Danziger, O., Shai, B., Sabo, Y., Bacharach, E. & Ehrlich, M. Combined genetic and epigenetic interferences with interferon signaling expose prostate cancer cells to viral infection. Oncotarget 7, 52115–52134 (2016).
DeWeese, T. L. et al. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Res. 61, 7464–7472 (2001).
Small, E. J. et al. A phase I trial of intravenous CG7870, a replication-selective, prostate-specific antigen-targeted oncolytic adenovirus, for the treatment of hormone-refractory, metastatic prostate cancer. Mol. Ther. 14, 107–117 (2006).
Freytag, S. O., Barton, K. N. & Zhang, Y. Efficacy of oncolytic adenovirus expressing suicide genes and interleukin-12 in preclinical model of prostate cancer. Gene Ther. 20, 1131–1139 (2013).
Freytag, S. O. et al. Five-year follow-up of trial of replication-competent adenovirus-mediated suicide gene therapy for treatment of prostate cancer. Mol. Ther. 15, 636–642 (2007).
Freytag, S. O. et al. Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res. 62, 4968–4976 (2002).
Fukuhara, H., Homma, Y. & Todo, T. Oncolytic virus therapy for prostate cancer. Int. J. Urol. 17, 20–30 (2010).
Arulanandam, R. et al. VEGF-mediated induction of PRD1-BF1/Blimp1 expression sensitizes tumor vasculature to oncolytic virus infection. Cancer Cell. 28, 210–224 (2015).
Ilkow, C. S. et al. Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity. Nat. Med. 21, 530–536 (2015).
Breitbach, C. J. et al. Targeting tumor vasculature with an oncolytic virus. Mol. Ther. 19, 886–894 (2011).
Lucas, T. et al. Adenoviral-mediated endothelial precursor cell delivery of soluble CD115 suppresses human prostate cancer xenograft growth in mice. Stem Cells 27, 2342–2352 (2009).
Passer, B. J. et al. Combination of vinblastine and oncolytic herpes simplex virus vector expressing IL-12 therapy increases antitumor and antiangiogenic effects in prostate cancer models. Cancer Gene Ther. 20, 17–24 (2013).
Jha, B. K., Dong, B., Nguyen, C. T., Polyakova, I. & Silverman, R. H. Suppression of antiviral innate immunity by sunitinib enhances oncolytic virotherapy. Mol. Ther. 21, 1749–1757 (2013).
Munz, C., Lunemann, J. D., Getts, M. T. & Miller, S. D. Antiviral immune responses: triggers of or triggered by autoimmunity? Nat. Rev. Immunol. 9, 246–258 (2009).
Getts, D. R., Chastain, E. M., Terry, R. L. & Miller, S. D. Virus infection, antiviral immunity, and autoimmunity. Immunol. Rev. 255, 197–209 (2013).
Thirukkumaran, C. M. et al. Oncolytic viral therapy for prostate cancer: efficacy of reovirus as a biological therapeutic. Cancer Res. 70, 2435–2444 (2010).
Varghese, S. et al. Enhanced therapeutic efficacy of IL-12, but not GM-CSF, expressing oncolytic herpes simplex virus for transgenic mouse derived prostate cancers. Cancer Gene Ther. 13, 253–265 (2006).
Fong, L., Ruegg, C. L., Brockstedt, D., Engleman, E. G. & Laus, R. Induction of tissue-specific autoimmune prostatitis with prostatic acid phosphatase immunization: implications for immunotherapy of prostate cancer. J. Immunol. 159, 3113–3117 (1997).
Kottke, T. et al. Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors. Nat. Med. 17, 854–859 (2011).
Castelo-Branco, P. et al. Oncolytic herpes simplex virus armed with xenogeneic homologue of prostatic acid phosphatase enhances antitumor efficacy in prostate cancer. Gene Ther. 17, 805–810 (2010).
Kim, Y. et al. Dendritic cells in oncolytic virus-based anti-cancer therapy. Viruses 7, 6506–6525 (2015).
Komaru, A. et al. Sustained and NK/CD4+ T cell-dependent efficient prevention of lung metastasis induced by dendritic cells harboring recombinant Sendai virus. J. Immunol. 183, 4211–4219 (2009).
Kruslin, B., Tomas, D., Dzombeta, T., Milkovic-Perisa, M. & Ulamec, M. Inflammation in prostatic hyperplasia and carcinoma-basic scientific approach. Front. Oncol. 7, 77 (2017).
Schenk, J. M. et al. Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am. J. Epidemiol. 171, 571–582 (2010).
Gurel, B. et al. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol. Biomarkers Prev. 23, 847–856 (2014).
Hsing, A. W., Tsao, L. & Devesa, S. S. International trends and patterns of prostate cancer incidence and mortality. Int. J. Cancer 85, 60–67 (2000).
Vidal, A. C. et al. Racial differences in prostate inflammation: results from the REDUCE study. Oncotarget 8, 71393–71399 (2016).
Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860–867 (2002).
Adler, H. L. et al. Elevated levels of circulating interleukin-6 and transforming growth factor-beta1 in patients with metastatic prostatic carcinoma. J. Urol. 161, 182–187 (1999).
Yang, Y. F. et al. Antitumor effects of oncolytic adenovirus armed with PSA-IZ-CD40L fusion gene against prostate cancer. Gene Ther. 21, 723–731 (2014).
Moussavi, M. et al. Targeting and killing of metastatic cells in the transgenic adenocarcinoma of mouse prostate model with vesicular stomatitis virus. Mol. Ther. 21, 842–848 (2013).
Seyedin, S. N. et al. Strategies for combining immunotherapy with radiation for anticancer therapy. Immunotherapy 7, 967–980 (2015).
Nguyen, A., Ho, L. & Wan, Y. Chemotherapy and oncolytic virotherapy: advanced tactics in the war against cancer. Front. Oncol. 4, 145 (2014).
Galluzzi, L., Bravo-San Pedro, J. M., Demaria, S., Formenti, S. C. & Kroemer, G. Activating autophagy to potentiate immunogenic chemotherapy and radiation therapy. Nat. Rev. Clin. Oncol. 14, 247–258 (2017).
Galluzzi, L., Senovilla, L., Zitvogel, L. & Kroemer, G. The secret ally: immunostimulation by anticancer drugs. Nat. Rev. Drug Discov. 11, 215–233 (2012).
Cao, W. et al. Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway. Nat. Immunol. 9, 1157–1164 (2008).
Olagnier, D. et al. Activation of Nrf2 signaling augments vesicular stomatitis virus oncolysis via autophagy-driven suppression of antiviral immunity. Mol. Ther. 25, 1900–1916 (2017).
Garg, A. D. & Agostinis, P. Cell death and immunity in cancer: From danger signals to mimicry of pathogen defense responses. Immunol. Rev. 280, 126–148 (2017).
Meng, S., Xu, J., Wu, Y. & Ding, C. Targeting autophagy to enhance oncolytic virus-based cancer therapy. Expert Opin. Biol. Ther. 13, 863–873 (2013).
Passer, B. J. et al. Oncolytic herpes simplex virus vectors and taxanes synergize to promote killing of prostate cancer cells. Cancer Gene Ther. 16, 551–560 (2009).
Nielsen, L. L., Lipari, P., Dell, J., Gurnani, M. & Hajian, G. Adenovirus-mediated p53 gene therapy and paclitaxel have synergistic efficacy in models of human head and neck, ovarian, prostate, and breast cancer. Clin. Cancer Res. 4, 835–846 (1998).
Yu, D. C. et al. Antitumor synergy of CV787, a prostate cancer-specific adenovirus, and paclitaxel and docetaxel. Cancer Res. 61, 517–525 (2001).
Fehl, D. J. & Ahmed, M. Curcumin promotes the oncoltyic capacity of vesicular stomatitis virus for the treatment of prostate cancers. Virus Res. 228, 14–23 (2017).
Hodzic, J., Sie, D., Vermeulen, A. & van Beusechem, V. W. Functional screening identifies human miRNAs that modulate adenovirus propagation in prostate cancer cells. Hum. Gene Ther. 28, 766–780 (2017).
Mansfield, D. C. et al. Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer. Gene Ther. 23, 357–368 (2016).
Trujillo, M. A., Oneal, M. J., McDonough, S., Qin, R. & Morris, J. C. A steep radioiodine dose response scalable to humans in sodium-iodide symporter (NIS)-mediated radiovirotherapy for prostate cancer. Cancer Gene Ther. 19, 839–844 (2012).
Muthana, M. et al. Macrophage delivery of an oncolytic virus abolishes tumor regrowth and metastasis after chemotherapy or irradiation. Cancer Res. 73, 490–495 (2013).
Galluzzi, L., Buque, A., Kepp, O., Zitvogel, L. & Kroemer, G. Immunogenic cell death in cancer and infectious disease. Nat. Rev. Immunol. 17, 97–111 (2017).
Gujar, S. A., Clements, D. & Lee, P. W. Two is better than one: Complementing oncolytic virotherapy with gemcitabine to potentiate antitumor immune responses. Oncoimmunology 3, e27622 (2014).
Gujar, S. A. et al. Gemcitabine enhances the efficacy of reovirus-based oncotherapy through anti-tumour immunological mechanisms. Br. J. Cancer 110, 83–93 (2014).
Schirrmacher, V., Bihari, A. S., Stucker, W. & Sprenger, T. Long-term remission of prostate cancer with extensive bone metastases upon immuno- and virotherapy: a case report. Oncol. Lett. 8, 2403–2406 (2014).
Jiang, H., Lin, J. J., Su, Z. Z., Goldstein, N. I. & Fisher, P. B. Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression. Oncogene 11, 2477–2486 (1995).
Sarkar, D. et al. Eradication of therapy-resistant human prostate tumors using a cancer terminator virus. Cancer Res. 67, 5434–5442 (2007).
Sarkar, S. et al. Novel therapy of prostate cancer employing a combination of viral-based immunotherapy and a small molecule BH3 mimetic. Oncoimmunology 5, e1078059 (2015).
Pradhan, A. K. et al. mda-7/IL-24 mediates cancer cell-specific death via regulation of miR-221 and the Beclin-1 axis. Cancer Res. 77, 949–959 (2017).
Su, Z. Z. et al. Ionizing radiation enhances therapeutic activity of mda-7/IL-24: overcoming radiation- and mda-7/IL-24-resistance in prostate cancer cells overexpressing the antiapoptotic proteins bcl-xL or bcl-2. Oncogene 25, 2339–2348 (2006).
Lebedeva, I. V. et al. Strategy for reversing resistance to a single anticancer agent in human prostate and pancreatic carcinomas. Proc. Natl Acad. Sci. USA 104, 3484–3489 (2007).
Fukuhara, H., Ino, Y., Kuroda, T., Martuza, R. L. & Todo, T. Triple gene-deleted oncolytic herpes simplex virus vector double-armed with interleukin 18 and soluble B7-1 constructed by bacterial artificial chromosome-mediated system. Cancer Res. 65, 10663–10668 (2005).
Varghese, S., Rabkin, S. D., Nielsen, P. G., Wang, W. & Martuza, R. L. Systemic oncolytic herpes virus therapy of poorly immunogenic prostate cancer metastatic to lung. Clin. Cancer Res. 12, 2919–2927 (2006).
Liu, C., Hasegawa, K., Russell, S. J., Sadelain, M. & Peng, K. W. Prostate-specific membrane antigen retargeted measles virotherapy for the treatment of prostate cancer. Prostate 69, 1128–1141 (2009).
Madan, R. A. et al. Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol. 13, 501–508 (2012).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01867333 (2017).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01875250 (2017).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02861573. (2017).
Harris, K. S. & Kerr, B. A. Prostate cancer stem cell markers drive progression, therapeutic resistance, and bone metastasis. Stem Cells Int. 2017, 8629234 (2017).
Velardi, E. et al. Sex steroid blockade enhances thymopoiesis by modulating Notch signaling. J. Exp. Med. 211, 2341–2349 (2014).
Goldberg, G. L. et al. Sex steroid ablation enhances lymphoid recovery following autologous hematopoietic stem cell transplantation. Transplantation 80, 1604–1613 (2005).
Tang, S. & Dubey, P. Opposing effects of androgen ablation on immune function in prostate cancer. Oncoimmunology 1, 1220–1221 (2012).
Tang, S., Moore, M. L., Grayson, J. M. & Dubey, P. Increased CD8+ T-cell function following castration and immunization is countered by parallel expansion of regulatory T cells. Cancer Res. 72, 1975–1985 (2012).
Kissick, H. T. et al. Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proc. Natl Acad. Sci. USA 111, 9887–9892 (2014).
Pu, Y. et al. Androgen receptor antagonists compromise T cell response against prostate cancer leading to early tumor relapse. Sci. Transl Med. 8, 333ra47 (2016).
Antonarakis, E. S. et al. Sequencing of Sipuleucel-T and androgen deprivation therapy in men with hormone-sensitive biochemically recurrent prostate cancer: a phase II randomized trial. Clin. Cancer Res. 23, 2451–2459 (2017).
Gamat, M. & McNeel, D. G. Androgen deprivation and immunotherapy for the treatment of prostate cancer. Endocr. Relat. Cancer 24, T297–T310 (2017).
Akira, S., Saitoh, T. & Kawai, T. Nucleic acids recognition by innate immunity. Uirusu 62, 39–45 (2012).
Alemany, R. & Cascallo, M. Oncolytic viruses from the perspective of the immune system. Future Microbiol. 4, 527–536 (2009).
Barker, H. E., Paget, J. T., Khan, A. A. & Harrington, K. J. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat. Rev. Cancer. 15, 409–425 (2015).
Murphy, J. P. et al. MHC-I ligand discovery using targeted database searches of mass spectrometry data: implications for T-cell immunotherapies. J. Proteome Res. 16, 1806–1816 (2017).
Nielsen, M. & Andreatta, M. NetMHCpan- 3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets. Genome Med. 8, 33 (2016).
Croft, N. P., Purcell, A. W. & Tscharke, D. C. Quantifying epitope presentation using mass spectrometry. Mol. Immunol. 68, 77–80 (2015).
Yadav, M. et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature 515, 572–576 (2014).
Comber, J. D. & Philip, R. MHC class I antigen presentation and implications for developing a new generation of therapeutic vaccines. Ther. Adv. Vaccines 2, 77–89 (2014).
Serganova, I. et al. Enhancement of PSMA-directed CAR adoptive immunotherapy by PD-1/PD-L1 blockade. Mol. Ther. Oncolyt. 4, 41–54 (2016).
Amin Al Olama, A. et al. Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans. Hum. Mol. Genet. 24, 5589–5602 (2015).
Fraser, M. et al. Genomic hallmarks of localized, non-indolent prostate cancer. Nature 541, 359–364 (2017).
Cancer Genome Atlas Research Network. The molecular taxonomy of primary prostate cancer. Cell 163, 1011–1025 (2015).
Boutros, P. C. et al. Spatial genomic heterogeneity within localized, multifocal prostate cancer. Nat. Genet. 47, 736–745 (2015).
Chosey, L. C. et al. Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th edn (U.S. Department of Health and Human Services, 2009).
Hoos, A., Wolchok, J. D., Humphrey, R. W. & Hodi, F. S. CCR 20th Anniversary Commentary: Immune-related response criteria — capturing clinical activity in immuno-oncology. Clin. Cancer Res. 21, 4989–4991 (2015).
Freytag, S. O. et al. Prospective randomized phase 2 trial of intensity modulated radiation therapy with or without oncolytic adenovirus-mediated cytotoxic gene therapy in intermediate-risk prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 89, 268–276 (2014).
Pol, J. et al. Trial Watch — Oncolytic viruses and cancer therapy. Oncoimmunology 5, e1117740 (2015).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02555397 (2016).
[No authors listed.] UMIN-CTR Clinical Trial UMIN000010463. University Hospital Information Network https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000012228&language=E (2016).
Vidal, L. et al. A phase I study of intravenous oncolytic reovirus type 3 Dearing in patients with advanced cancer. Clin. Cancer Res. 14, 7127–7137 (2008).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01619813 (2016).
[No authors listed.] UMIN-CTR Clinical Trial UMIN000010840. University Hospital Information Network https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000012688&language=E (2016).
Lei, N. et al. An oncolytic adenovirus expressing granulocyte macrophage colony-stimulating factor shows improved specificity and efficacy for treating human solid tumors. Cancer Gene Ther. 16, 33–43 (2009).
Huang, X. F. et al. A broadly applicable, personalized heat shock protein-mediated oncolytic tumor vaccine. Cancer Res. 63, 7321–7329 (2003).
Li, J. L. et al. A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients. Gene Ther. 16, 376–382 (2009).
Kaufman, H. L. et al. Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): a trial of the Eastern Cooperative Oncology Group. J. Clin. Oncol. 22, 2122–2132 (2004).
Madan, R. A., Arlen, P. M., Mohebtash, M., Hodge, J. W. & Gulley, J. L. Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer. Expert Opin. Investig. Drugs 18, 1001–1011 (2009).
Fukuhara, H., Martuza, R. L., Rabkin, S. D., Ito, Y. & Todo, T. Oncolytic herpes simplex virus vector g47delta in combination with androgen ablation for the treatment of human prostate adenocarcinoma. Clin. Cancer Res. 11, 7886–7890 (2005).
Parato, K. A. et al. The oncolytic poxvirus JX-594 selectively replicates in and destroys cancer cells driven by genetic pathways commonly activated in cancers. Mol. Ther. 20, 749–758 (2012).
Moussavi, M. et al. Oncolysis of prostate cancers induced by vesicular stomatitis virus in PTEN knockout mice. Cancer Res. 70, 1367–1376 (2010).