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.

  • Article
  • Published:

Netrin-1 blockade inhibits tumor associated Myeloid-derived suppressor cells, cancer stemness and alleviates resistance to chemotherapy and immune checkpoint inhibitor

Cell Death & Differentiation volume 30, pages 2201–2212 (2023)Cite this article

Subjects

Abstract

Drug resistance and cancer relapse represent significant therapeutic challenges after chemotherapy or immunotherapy, and a major limiting factor for long-term cancer survival. Netrin-1 was initially identified as a neuronal navigation cue but has more recently emerged as an interesting target for cancer therapy, which is currently clinically investigated. We show here that netrin-1 is an independent prognostic marker for clinical progression of breast and ovary cancers. Cancer stem cells (CSCs)/Tumor initiating cells (TICs) are hypothesized to be involved in clinical progression, tumor relapse and resistance. We found a significant correlation between netrin-1 expression and cancer stem cell (CSC) markers levels. We also show in different mice models of resistance to chemotherapies that netrin-1 interference using a therapeutic netrin-1 blocking antibody alleviates resistance to chemotherapy and triggers an efficient delay in tumor relapse and this effect is associated with CSCs loss. We also demonstrate that netrin-1 interference limits tumor resistance to immune checkpoint inhibitor and provide evidence linking this enhanced anti-tumor efficacy to a decreased recruitment of a subtype of myeloid-derived suppressor cells (MDSCs) called polymorphonuclear (PMN)-MDSCs. We have functionally demonstrated that these immune cells promote CSCs features and, consequently, resistance to anti-cancer treatments. Together, these data support the view of both a direct and indirect contribution of netrin-1 to cancer stemness and we propose that this may lead to therapeutic opportunities by combining conventional chemotherapies and immunotherapies with netrin-1 interfering drugs.

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: Netrin-1 expression is a poor prognosis marker and correlates with stem cells marker in human breast and ovary cancers.
Fig. 2: Netrin-1 expression is associated with CSCs features in human cell lines and in a PDX model of breast cancer resistance to chemotherapy.
Fig. 3: Netrin-1 blockade delays cancer relapse and impact CSCs features.
Fig. 4: Netrin-1 blockade alleviates resistance to immune checkpoint inhibitor anti-CTLA-4.
Fig. 5: Netrin-1 blockade efficiently impacts CSCs/TICs untargeted by anti-CTLA-4 mAb.

Similar content being viewed by others

References

  1. Serafini T, Colamarino SA, Leonardo ED, Wang H, Beddington R, Skarnes WC, et al. Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system. Cell. 1996;87:1001–14.

    Article  CAS  PubMed  Google Scholar 

  2. Chédotal A. Roles of axon guidance molecules in neuronal wiring in the developing spinal cord. Nat Rev Neurosci. 2019;20:380–96.

    Article  PubMed  Google Scholar 

  3. Mehlen P, Delloye-Bourgeois C, Chédotal A. Novel roles for slits and netrins: axon guidance cues as anticancer targets? Nat Rev Cancer. 2011;11:188–97.

    Article  CAS  PubMed  Google Scholar 

  4. Mehlen P, Bredesen DE. Dependence receptors: from basic research to drug development. Sci Signal. 2011;4:mr2.

    Article  PubMed  Google Scholar 

  5. Bongo JB, Peng DQ. The neuroimmune guidance cue netrin-1: a new therapeutic target in cardiovascular disease. J Cardiol. 2014;63:95–8.

    Article  PubMed  Google Scholar 

  6. van Gils JM, Derby MC, Fernandes LR, Ramkhelawon B, Ray TD, Rayner KJ, et al. The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques. Nat Immunol. 2012;13:136–43.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ramkhelawon B, Hennessy EJ, Ménager M, Ray TD, Sheedy FJ, Hutchison S, et al. Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity. Nat Med. 2014;20:377–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sanvoranart T, Supokawej A, Kheolamai P, U-pratya Y, Poungvarin N, Sathornsumetee S, et al. Targeting Netrin-1 in glioblastoma stem-like cells inhibits growth, invasion, and angiogenesis. Tumor Biol. 2016;37:14949–60.

    Article  CAS  Google Scholar 

  9. Barnault R, Verzeroli C, Fournier C, Michelet M, Redavid AR, Chicherova I, et al. Hepatic inflammation elicits production of proinflammatory netrin‐1 through exclusive activation of translation. Hepatology. 2022;76:1346–59.

  10. Fazeli A, Dickinson SL, Hermiston ML, Tighe RV, Steen RG, Small CG, et al. Phenotype of mice lacking functional deleted in colorectal cancer (Dcc) gene. Nature. 1997;386:796–804.

    Article  CAS  PubMed  Google Scholar 

  11. Leonardo ED, Hinck L, Masu M, Keino-Masu K, Ackerman SL, Tessier-Lavigne M. Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors. Nature. 1997;386:833–8.

    Article  CAS  PubMed  Google Scholar 

  12. Gibert B, Mehlen P. Dependence receptors and cancer: addiction to trophic ligands. Cancer Res. 2015;75:5171–5.

    Article  CAS  PubMed  Google Scholar 

  13. Fitamant J, Guenebeaud C, Coissieux M-M, Guix C, Treilleux I, Scoazec J-Y, et al. Netrin-1 expression confers a selective advantage for tumor cell survival in metastatic breast cancer. Proc Natl Acad Sci. 2008;105:4850–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Delloye-Bourgeois C, Fitamant J, Paradisi A, Cappellen D, Douc-Rasy S, Raquin M-A, et al. Netrin-1 acts as a survival factor for aggressive neuroblastoma. J Exp Med. 2009;206:833–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Delloye-Bourgeois C, Brambilla E, Coissieux M-M, Guenebeaud C, Pedeux R, Firlej V, et al. Interference with netrin-1 and tumor cell death in non-small cell lung cancer. J Natl Cancer Inst. 2009;101:237–47.

    Article  CAS  PubMed  Google Scholar 

  16. Paradisi A, Creveaux M, Gibert B, Devailly G, Redoulez E, Neves D, et al. Combining chemotherapeutic agents and netrin-1 interference potentiates cancer cell death. EMBO Mol Med. 2013;5:1821–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Grandin M, Meier M, Delcros JG, Nikodemus D, Reuten R, Patel TR, et al. Structural decoding of the Netrin-1/UNC5 interaction and its therapeutical implications in cancers. Cancer Cell. 2016;29:173–85.

    Article  CAS  PubMed  Google Scholar 

  18. Kryza D, Wischhusen J, Richaud M, Hervieu M, Sidi Boumedine J, Delcros J, et al. From netrin‐1‐targeted SPECT/CT to internal radiotherapy for management of advanced solid tumors. EMBO Mol Med. 2023;15:e16732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cassier P, Eberst L, Garin G, Courbebaisse Y, Terret C, Robert M, et al. A first in human, phase I trial of NP137, a first-in-class antibody targeting netrin-1, in patients with advanced refractory solid tumors. Ann Oncol. 2019;30:v159.

    Article  Google Scholar 

  20. Cassier PA, Navaridas R, Bellina M, Rama N, Ducarouge B, Hernandez-Vargas H, et al. Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer. Nature. 2023. https://doi.org/10.1038/s41586-023-06367-z.

  21. Lengrand J, Pastushenko I, Vanuytven S, Song Y, Venet D, Sarate RM, et al. Pharmacological targeting of netrin-1 inhibits EMT in cancer. Nature. 2023. https://doi.org/10.1038/s41586-023-06372-2.

  22. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.

    Article  CAS  PubMed  Google Scholar 

  23. Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF. Cancer stem cells from colorectal cancer-derived cell lines. Proc Natl Acad Sci USA. 2010;107:3722–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Miao Y, Yang H, Levorse J, Yuan S, Polak L, Sribour M, et al. Adaptive immune resistance emerges from tumor-initiating stem cells. Cell. 2019;177:1172–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lu H, Xie Y, Tran L, Lan J, Yang Y, Murugan NL, et al. Chemotherapy-induced S100A10 recruits KDM6A to facilitate OCT4-mediated breast cancer stemness. J Clin Investig. 2020. https://doi.org/10.1172/JCI138577.

  26. Batlle E, Clevers H. Cancer stem cells revisited. Nat Med. 2017;23:1124–34.

    Article  CAS  PubMed  Google Scholar 

  27. Ye L, Lin C, Wang X, Li Q, Li Y, Wang M, et al. Epigenetic silencing of SALL 2 confers tamoxifen resistance in breast cancer. EMBO Mol Med. 2019;11. https://doi.org/10.15252/emmm.201910638.

  28. Arfaoui A, Rioualen C, Azzoni V, Pinna G, Finetti P, Wicinski J, et al. A genome‐wide RNA i screen reveals essential therapeutic targets of breast cancer stem cells. EMBO Mol Med. 2019;11. https://doi.org/10.15252/emmm.201809930.

  29. Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501:346–54.

    Article  CAS  PubMed  Google Scholar 

  30. Papanastasiou AD, Pampalakis G, Katsaros D, Sotiropoulou G. Netrin-1 overexpression is predictive of ovarian malignancies. Oncotarget. 2011;2:363–7.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Charafe-Jauffret E, Ginestier C, Iovino F, Tarpin C, Diebel M, Esterni B, et al. Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res. 2010;16:45–55.

    Article  CAS  PubMed  Google Scholar 

  33. Marangoni E, Lecomte N, Durand L, de Pinieux G, Decaudin D, Chomienne C, et al. CD44 targeting reduces tumour growth and prevents post-chemotherapy relapse of human breast cancers xenografts. Br J Cancer. 2009;100:918–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dumartin L, Quemener C, Laklai H, Herbert J, Bicknell R, Bousquet C, et al. Netrin-1 mediates early events in pancreatic adenocarcinoma progression, acting on tumor and endothelial cells. Gastroenterology. 2010;138:1595–606.

    Article  CAS  PubMed  Google Scholar 

  35. Dongre A, Rashidian M, Reinhardt F, Bagnato A, Keckesova Z, Ploegh HL, et al. Epithelial-to-mesenchymal transition contributes to immunosuppression in breast carcinomas. Cancer Res. 2017;77:3982–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bayraktar S, Batoo S, Okuno S, Glück S. Immunotherapy in breast cancer. J Carcinog. 2019;18:2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Polk A, Svane I-M, Andersson M, Nielsen D. Checkpoint inhibitors in breast cancer – current status. Cancer Treat Rev. 2018;63:122–34.

    Article  CAS  PubMed  Google Scholar 

  38. Read S, Greenwald R, Izcue A, Robinson N, Mandelbrot D, Francisco L, et al. Blockade of CTLA-4 on CD4 + CD25 + regulatory T cells abrogates their function in vivo. J Immunol. 2006;177:4376–83.

    Article  CAS  PubMed  Google Scholar 

  39. Ni L, Lu J. Interferon gamma in cancer immunotherapy. Cancer Med. 2018;7:4509–16.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Zhou J, Nefedova Y, Lei A, Gabrilovich D. Neutrophils and PMN-MDSC: their biological role and interaction with stromal cells. Semin Immunol. 2018;35:19–28.

    Article  CAS  PubMed  Google Scholar 

  41. Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ. Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci. 1992;89:10578–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Peng D, Tanikawa T, Li W, Zhao L, Vatan L, Szeliga W, et al. Myeloid-derived suppressor cells endow stem-like qualities to breast cancer cells through IL6/STAT3 and NO/NOTCH cross-talk signaling. Cancer Res. 2016;76:3156–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ozmadenci D, Féraud O, Markossian S, Kress E, Ducarouge B, Gibert B, et al. Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance. Nat Commun. 2015;6:7398.

    Article  PubMed  Google Scholar 

  44. Huyghe A, Furlan G, Ozmadenci D, Galonska C, Charlton J, Gaume X, et al. Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signalling. Nat Cell Biol. 2020;22:389–400.

    Article  CAS  PubMed  Google Scholar 

  45. Renders S, Svendsen AF, Panten J, Rama N, Maryanovich M, Sommerkamp P, et al. Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1. Nat Commun. 2021;12:608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Boneschansker L, Nakayama H, Eisenga M, Wedel J, Klagsbrun M, Irimia D, et al. Netrin-1 augments chemokinesis in CD4+ T cells in vitro and elicits a proinflammatory response in vivo. J Immunol. 2016;197:1389–98.

    Article  CAS  PubMed  Google Scholar 

  47. Lu W, Yu W, He J, Liu W, Yang J, Lin X, et al. Reprogramming immunosuppressive myeloid cells facilitates immunotherapy for colorectal cancer. EMBO Mol Med. 2021;13. https://doi.org/10.15252/emmm.202012798.

  48. Sung P-J, Rama N, Imbach J, Fiore S, Ducarouge B, Neves D, et al. Cancer-associated fibroblasts produce netrin-1 to control cancer cell plasticity. Cancer Res. 2019;79:3651–61.

    Article  CAS  PubMed  Google Scholar 

  49. Thakore PI, D’Ippolito AM, Song L, Safi A, Shivakumar NK, Kabadi AM, et al. Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements. Nat Methods. 2015;12:1143–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mieulet V, Garnier C, Kieffer Y, Guilbert T, Nemati F, Marangoni E, et al. Stiffness increases with myofibroblast content and collagen density in mesenchymal high grade serous ovarian cancer. Sci Rep. 2021;11:4219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gibert B, Delloye-Bourgeois C, Gattolliat C-H, Meurette O, Le Guernevel S, Fombonne J, et al. Regulation by miR181 family of the dependence receptor CDON tumor suppressive activity in neuroblastoma. J Natl Cancer Inst. 2014;106. https://doi.org/10.1093/jnci/dju318.

  52. Jiang S, Richaud M, Vieugué P, Rama N, Delcros J, Siouda M, et al. Targeting netrin‐3 in small cell lung cancer and neuroblastoma. EMBO Mol Med. 2021. https://doi.org/10.15252/emmm.202012878.

Download references

Acknowledgements

We thank Dwayne Stupack for correction and helpful discussion, the LMT platform for the high quality of the animal work. This work was supported by Netris Pharma and institutional grants from CNRS (PM, BG), University of Lyon (PM), Centre Léon Bérard (PM) and from the Ligue Contre le Cancer (PM), INCA (PM), Euronanomed (PM, BG), ANR (PM), BMS Foundation for Immunotherapy (PM). AR received a 4th year fellowship from Ligue contre le Cancer.

Author information

Author notes

  1. These authors contributed equally: Benjamin Ducarouge, Anna-Rita Redavid.

  2. These authors jointly supervised this work: Benjamin Gibert, Patrick Mehlen, Agnes Bernet.

Authors and Affiliations

  1. Apoptosis, Cancer and Development Laboratory- Equipe labellisée ‘La Ligue’, Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France

    Benjamin Ducarouge, Anna-Rita Redavid, Camille Victoor, Ruxanda Chira, Maëva Hervieu, Roméo Bergé, Justine Lengrand, Pauline Vieugué, Isabelle Goddard, Mathieu Richaud, Pierre-Alexandre Laval, Nicolas Rama, Andrea Paradisi, Benjamin Gibert, Patrick Mehlen & Agnes Bernet

  2. Netris Pharma, Centre Léon Bérard, 69008, Lyon, France

    Benjamin Ducarouge, Camille Victoor, Ruxanda Chira, Roméo Bergé, Justine Lengrand, David Neves, David Goldschneider, Stéphane Depil, Patrick Mehlen & Agnes Bernet

  3. Research Pathology Department, Centre Léon Bérard, Lyon, France

    Aurélien Fonseca

  4. Targeting of the Tumor and its Immune Environnement, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France

    Nicolas Gourdin

  5. UBET, Centre Léon Bérard, Lyon, France

    Sylvie Chabaud & Isabelle Treilleux

  6. Pathology Department, Centre Léon Bérard, Lyon, France

    Nicolas Gadot, Isabelle Ray-Coquard & Séverine Tabone-Eglinger

  7. Laboratory of Preclinical Investigations, Translational Research Department, Institut Curie, Université Paris-Sciences-et-Lettres, 75005, Paris, France

    Didier Decaudin, Fariba Némati & Elisabetta Marangoni

  8. Department of Pathology, IUCT Oncopole, Toulouse, France

    Eliane Mery-Lamarche

  9. Department of Pathology, Gustave Roussy, Villejuif, France

    Catherine Génestie

  10. Department of Pathology, Hospices Civils de Lyon, 69002, Lyon, France

    Mojgan Devouassoux-Shisheboran

  11. Department of Medicine, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA

    Kathryn J. Moore

Authors
  1. Benjamin Ducarouge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna-Rita Redavid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Camille Victoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ruxanda Chira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aurélien Fonseca
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maëva Hervieu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Roméo Bergé
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Justine Lengrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pauline Vieugué
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. David Neves
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Isabelle Goddard
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mathieu Richaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Pierre-Alexandre Laval
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Nicolas Rama
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. David Goldschneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Andrea Paradisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Nicolas Gourdin
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Sylvie Chabaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Isabelle Treilleux
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Nicolas Gadot
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Isabelle Ray-Coquard
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Stéphane Depil
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Didier Decaudin
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Fariba Némati
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Elisabetta Marangoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Eliane Mery-Lamarche
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Catherine Génestie
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Séverine Tabone-Eglinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Mojgan Devouassoux-Shisheboran
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Kathryn J. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Benjamin Gibert
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Patrick Mehlen
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. Agnes Bernet
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BD, ARR, CV, RC, RB, AP and JL performed the cell experiments and in vitro data; BD, ARR, MH, PV, DN, MR, IG, FN and PAL performed mice experiments; CV, RB, AP and DG produced the lentiviruses and CRISPR and Sh cell lines; BD, AF, IT and NG made anatomopathological analysis; NR performed bioinformatical analysis; NG, IT, IRC, EML, CG, STE and MDS provided human samples and cell lines; BD, ARR and SC performed statistical analysis; BD, ARR, SD, DD, EM, KJM, BG, PM and AB have participated to the research design and to write the paper.

Corresponding authors

Correspondence to Benjamin Gibert, Patrick Mehlen or Agnes Bernet.

Ethics declarations

Competing interests

BD, CV, JL, DN, DG, SD, AB and PM declare to have a conflict of interest as respectively employees (BD, DN, DG, CV, JL and SD) and shareholders (AB and PM) of NETRIS Pharma.

Additional information

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

Supplementary information

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

Ducarouge, B., Redavid, AR., Victoor, C. et al. Netrin-1 blockade inhibits tumor associated Myeloid-derived suppressor cells, cancer stemness and alleviates resistance to chemotherapy and immune checkpoint inhibitor. Cell Death Differ 30, 2201–2212 (2023). https://doi.org/10.1038/s41418-023-01209-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41418-023-01209-x

Search

Advanced search

Quick links