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From foes to friends: rethinking the role of lymph nodes in prostate cancer

Nature Reviews Urology (2024)Cite this article

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Abstract

Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes. Thus, whether lymph nodes are truly ‘foes’ or whether they are actually ‘friends’ in oncological care is an important idea to discuss.

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Fig. 1: Pelvic lymph node stations.
Fig. 2: The role of lymphatics in promoting cancer cell dissemination.
Fig. 3: The cancer–immunity cycle and prostate cancer.
Fig. 4: A novel schema for the categorization of pelvic lymph nodes.

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Acknowledgements

The authors thank T. P. Padera for his kind review of and contributions to the intellectual content contained within this manuscript. They thank B. Halasz for her help conceptualizing the figures.

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Authors and Affiliations

  1. Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Raghav Gupta, Chandan K. Das, Sujit S. Nair, Adriana Marcela Pedraza-Bermeo, Ali H. Zahalka, Natasha Kyprianou & Ashutosh K. Tewari

  2. Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Nina Bhardwaj

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Contributions

R.G., C.K.D. and S.S.N. researched data for the article. R.G., C.K.D., S.S.N., A.M.P.-B. and A.K.T. contributed substantially to discussion of the content. R.G., C.K.D., S.S.N. and A.M.P.-B. wrote the article. A.H.Z., N.K., N.B. and A.K.T. reviewed and/or edited the manuscript before submission.

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Correspondence to Ashutosh K. Tewari.

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Competing interests

N.K. serves on the advisory board for Onconox Inc. and has received funding from the NCI/NIH for her grant: R01 CA232574-01A1. N.B. is an extramural member of the Parker Institute for Cancer Immunotherapy, Carisma Therapeutics, Curevac, Genotwin, Novartis, Primevax, Rome Therapeutics and Tempest Therapeutics. N.B. receives research funds from Dragonfly Therapeutics, Harbour Biomed Sciences, Regeneron Pharmaceuticals Inc. and the Ludwig Institute for Cancer Research. A.K.T. has served as a site-PI on sponsored clinical trials from Kite Pharma Inc., Lumicell Inc., Dendron Pharmaceuticals, LLC., Oncovir Inc., Blue Earth Diagnostics Ltd., RhoVac ApS., Bayer HealthCare Pharmaceuticals Inc. and Janssen Research and Development, LLC. A.K.T. has also served as an unpaid consultant to Roivant Biosciences and as an adviser to Promaxo. He owns equity in Promaxo. R.G., C.K.D., S.S.N., A.M.P.-B. and A.H.Z. declare no competing interests.

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Nature Reviews Urology thanks Marco Moschini and Masaki Shiota for their contribution to the peer review of this work.

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Gupta, R., Das, C.K., Nair, S.S. et al. From foes to friends: rethinking the role of lymph nodes in prostate cancer. Nat Rev Urol (2024). https://doi.org/10.1038/s41585-024-00912-9

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