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The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers

Nature Reviews Urology (2025)Cite this article

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Abstract

Adoptive cell therapy using tumour-infiltrating lymphocytes (TILs) has been a very successful model of enhancing immune-based therapies. Clinical benefits have been shown for patients with advanced melanoma, leading to the first FDA approval for this immune modality in 2024. Although clinical trials conducted decades ago for advanced renal-cell cancer did not show significant clinical benefits, recent advances in the TIL generation process, manipulation techniques, preparative regimens and combination with immune checkpoint inhibitors offer new hope for reexploring optimized TIL therapy for genitourinary cancers. The current landscape of TIL therapy has seen progress in TIL manufacturing, optimization and delivery methodologies that have the potential to improve the safety and efficacy of TIL therapy in the management of advanced genitourinary malignancies. Furthermore, innovative combination approaches and novel strategies could enhance the clinical viability of TIL therapy and warrant evaluation in clinical trials treating patients with genitourinary cancers.

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Fig. 1: The current process of TIL therapy.
Fig. 2: Strategies to optimize TIL therapy.
Fig. 3: Optimizing dosage, administration and specificity of TIL therapy.
Fig. 4: Challenges and potential solutions for TIL therapy in prostate, bladder and kidney cancers.

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Author notes

  1. These authors contributed equally: Shari Pilon-Thomas, Jad Chahoud.

Authors and Affiliations

  1. Immuno-Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Marine Potez & Shari Pilon-Thomas

  2. Genitourinary Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Gabriel Roman Souza, Philippe E. Spiess & Jad Chahoud

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  1. Marine Potez
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All authors researched data for the article, made substantial contributions to discussion of the content, wrote the manuscript, and reviewed and edited the manuscript before submission.

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Correspondence to Shari Pilon-Thomas or Jad Chahoud.

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Competing interests

J.C. declares consulting or advisory roles at AVEO, DAVA Pharmaceuticals, Pfizer, Exelixis, Eisai and Merck. P.E.S. declares honoraria at UptoDate. S.P.-T. is an inventor on intellectual property related to the proliferation and expansion of tumour-infiltrating lymphocytes (TILs) that Moffitt Cancer Center has licensed to Iovance Biotherapeutics. Moffitt has also licensed IP to Tuhura Biopharma. S.P.-T. is also listed as a co-inventor on a patent application with Provectus Biopharmaceuticals and participates in sponsored research agreements with Provectus Biopharmaceuticals, Celgene, Iovance Biotherapeutics, Intellia Therapeutics, Dyve Biosciences and Turnstone Biologics that are not related to this research. S.P.-T. has received consulting fees from Seagen, Morphogenesis and KSQ Therapeutics. The other authors declare no competing interests.

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Nature Reviews Urology thanks Marco Donia, who co-reviewed with Edoardo Dionisio; David Aggen; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Potez, M., Roman Souza, G., Spiess, P.E. et al. The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers. Nat Rev Urol (2025). https://doi.org/10.1038/s41585-025-01088-6

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