Adaptive Immunity in Genitourinary Cancers

Madhuri Koti (1) , Trinity Bivalacqua (2) , Peter Black (3) , Toni Cathomen (4) , Matthew Galsky (5) , James Gulley (6) , Molly Ingersoll (7, 8) , Ashish Kamat (9) , Wassim Kassouf (10) , D Robert Siemens (1) , Jianjun Gao (9)

1 Queen's University [Kingston, Canada]
2 University of Pennsylvania
3 University of British Columbia [Vancouver]
4 University of Freiburg [Freiburg]
5 MSSM - Icahn School of Medicine at Mount Sinai [New York]
6 NIH - National Institutes of Health [Bethesda, MD, USA]
7 IC UM3 (UMR 8104 / U1016) - Institut Cochin
8 Inflammation et immunité des muqueuses - Mucosal Inflammation and Immunity
9 The University of Texas M.D. Anderson Cancer Center [Houston]
10 MUHC - McGill University Health Center [Montreal]

Context While urothelial and renal cell cancers have exhibited modest responses to novel immune checkpoint inhibitors targeting the programmed death ligand 1 and its receptor, response rates in patients with prostate cancer have remained poor. The factors underlying suboptimal outcomes observed in patients treated with novel immunotherapies are still to be resolved. Objective To review the literature and describe the key adaptive immune physiological events associated with cancer progression and therapeutic response in genitourinary (GU) cancers. Evidence acquisition We performed a nonsystematic, collaborative narrative review to highlight recent advancements leading to the current state of knowledge on the critical mediators of antitumor adaptive immunity to GU cancers. Further, we discuss the findings on the pre- and post-treatment immunological events that either are unique to each of the three cancer types or exhibit overlapping clinical associations. Evidence synthesis Aging-associated immune function decline is a major factor underlying poor outcomes observed in patients treated with both conventional and novel immunotherapies. Other cancer immunobiological aspects associated with suboptimal responses in GU cancers include the overall tumor mutational burden, mutations in specific tumor suppressor/DNA damage repair genes (KDM6A, PTEN, STAG2, TP53, ATM, and BRCA2), and abundance of multiple functional states of adaptive immune cells and their spatiotemporal localization within the tumor immune microenvironment. Understanding these mechanisms may potentially lead to the development of prognostic and predictive biomarkers such as immune cell infiltration profiles and tertiary lymphoid structures (TLSs) that associate with variable clinical outcomes depending on the nature of the novel immunotherapeutic approach. Implementation of newer immune-monitoring technologies and improved preclinical modeling systems will augment our understanding of the host and tumor intrinsic factors contributing to the variability of responses to immunotherapies. Conclusions Despite the tremendous progress made in the understanding of dynamic and static adaptive immune elements within the tumor immune landscape, several knowledge gaps remain. A comprehensive knowledge thus gained will lead to precision immunotherapy, improved drug sequencing, and a therapeutic response. Patient summary We performed a collaborative review by a diverse group of experts in the field to examine our understanding of the events and crosstalk between cancer cells and the patient’s immune system that are associated with responses to novel immunotherapies. An evolving understanding of tumor-intrinsic and host-related immune alterations, both before and after therapy, will aid in the discovery of promising markers of responses to immunotherapy as well as the development of unique therapeutic approaches for the management of genitourinary cancers.

Mots clés: Bladder cancer; Genitourinary cancers; Immune checkpoint inhibitor; Kidney cancer; Prostate cancer; Tertiary lymphoid structure; Tumor immune microenvironment

Domaines: Sciences du Vivant [q-bio]

Madhuri Koti, Trinity Bivalacqua, Peter Black, Toni Cathomen, Matthew Galsky, et al.. Adaptive Immunity in Genitourinary Cancers. European Urology Oncology, 2023, pp.In Press, Corrected Proof. ⟨10.1016/j.euo.2023.03.002⟩. ⟨pasteur-04076274⟩