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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.

Keywords

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

Abbreviations

FDA

Food and Drug Administration

IO

Immuno-oncology

GU

Genitourinary

UC

Urothelial carcinoma

RCC

Renal cell carcinoma

PCa

Prostate cancer

TME

Tumor microenvironment

ICI

Immune checkpoint inhibitor

NMIBC

Non-muscle invasive bladder cancer

BCG

Bacillus Calmette-Guérin

PS

Performance status

CTLA-4

Cytotoxic T-lymphocyte antigen-4

PD-1

Programmed cell death protein-1

PD-L1

Programmed cell death-ligand 1

ORR

Objective response rate

IC

Tumor-infiltrating immune cells

mOS

Median overall survival

TC

Tumor cells

AEs

Adverse events

CPS

Combined positive score

OS

Overall survival

IFN

Interferon

GEP

Gene expression profiling

TCGA

The Cancer Genome Atlas

IDO1

Indoleamine 2,3-dioxygenase 1

PFS

Progression-free survival

MIBC

Muscle-invasive bladder cancer

mRCC

Metastatic renal cell carcinoma

HD-IL-2

High-dose interleukin-2

TKIs

Tyrosine kinase inhibitors

DC

Dendritic cell

(IMDC)

International Metastatic Renal Cell Carcinoma Database Consortium

Tregs

Regulatory T cells

RECIST

Response Evaluation Criteria in Solid Tumors

irRC

Immunerelated response criteria

mCRPC

Metastatic castrate-resistant prostate cancer

ADT

Androgen deprivation therapy

dMMR

Mismatch repair deficient

MSI-H

Microsatellite instability-high

Notes

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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