Targeting the Tumor Microenvironment with Immunotherapy for Genitourinary Malignancies

  • Ariel E. Marciscano
  • Ravi A. Madan
Genitourinary Cancers (N Agarwal, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Genitourinary Cancers

Opinion statement

Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies. Recently, cancer immunotherapy with immune checkpoint inhibitors has transformed the prognostic landscape leading to durable responses in a subset of urothelial carcinoma and renal cell carcinoma patients with traditionally poor prognosis. Despite this success, many patients fail to respond to immune checkpoint inhibitors and progression/relapse remains common. Furthermore, modest clinical activity has been observed with ICIs as a monotherapy in advanced PCa. As such, novel treatment approaches are warranted and improved biomarkers for patient selection and treatment response are desperately needed. Future efforts should focus on exploring synergistic and rational combinations that safely and effectively boost response rates and survival in genitourinary malignancies. Specific areas of interest include (1) evaluating the optimal sequencing, disease burden, and timing of immuno-oncology agents with other anti-cancer therapeutics and (2) validating novel biomarkers of response to immunotherapy to optimize patient selection and to identify individuals most likely to benefit from immunotherapy across the heterogenous spectrum of genitourinary malignancies.


Immunotherapy Bladder cancer Urothelial carcinoma Prostate cancer Renal cell carcinoma Kidney Tumor microenvironment 



Food and Drug Administration






Urothelial carcinoma


Renal cell carcinoma


Prostate cancer


Tumor microenvironment


Immune checkpoint inhibitor


Non-muscle invasive bladder cancer


Bacillus Calmette-Guérin


Performance status


Cytotoxic T-lymphocyte antigen-4


Programmed cell death protein-1


Programmed cell death-ligand 1


Objective response rate


Tumor-infiltrating immune cells


Median overall survival


Tumor cells


Adverse events


Combined positive score


Overall survival




Gene expression profiling


The Cancer Genome Atlas


Indoleamine 2,3-dioxygenase 1


Progression-free survival


Muscle-invasive bladder cancer


Metastatic renal cell carcinoma


High-dose interleukin-2


Tyrosine kinase inhibitors


Dendritic cell


International Metastatic Renal Cell Carcinoma Database Consortium


Regulatory T cells


Response Evaluation Criteria in Solid Tumors


Immunerelated response criteria


Metastatic castrate-resistant prostate cancer


Androgen deprivation therapy


Mismatch repair deficient


Microsatellite instability-high


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaUSA

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