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Review
. 2023 Dec 27;16(1):131.
doi: 10.3390/cancers16010131.

Current Landscape of Immune Checkpoint Inhibitors for Metastatic Urothelial Carcinoma: Is There a Role for Additional T-Cell Blockade?

Vanessa Ogbuji  1 , Irasema C Paster  1 , Alejandro Recio-Boiles  2 , Jennifer S Carew  2 , Steffan T Nawrocki  1   2 , Juan Chipollini  1
Affiliations
Review

Current Landscape of Immune Checkpoint Inhibitors for Metastatic Urothelial Carcinoma: Is There a Role for Additional T-Cell Blockade?

Vanessa Ogbuji et al. Cancers (Basel). .

Abstract

Urothelial carcinoma (UC) is the most common form of bladder cancer (BC) and is the variant with the most immunogenic response. This makes urothelial carcinoma an ideal candidate for immunotherapy with immune checkpoint inhibitors. Key immune checkpoint proteins PD-1 and CTLA-4 are frequently expressed on T-cells in urothelial carcinoma. The blockade of this immune checkpoint can lead to the reactivation of lymphocytes and augment the anti-tumor immune response. The only immune checkpoint inhibitors that are FDA-approved for metastatic urothelial carcinoma target the programmed death-1 receptor and its ligand (PD-1/PD-L1) axis. However, the overall response rate and progression-free survival rates of these agents are limited in this patient population. Therefore, there is a need to find further immune-bolstering treatment combinations that may positively impact survival for patients with advanced UC. In this review, the current immune checkpoint inhibition treatment landscape is explored with an emphasis on combination therapy in the form of PD-1/PD-L1 with CTLA-4 blockade. The investigation of the current literature on immune checkpoint inhibition found that preclinical data show a decrease in tumor volumes and size when PD-1/PD-L1 is blocked, and similar results were observed with CTLA-4 blockade. However, there are limited investigations evaluating the combination of CTLA-4 and PD-1/PD-L1 blockade. We anticipate this review to provide a foundation for a deeper experimental investigation into combination immune checkpoint inhibition therapy in metastatic urothelial carcinoma.

Keywords: CTLA-4; PD-1; bladder cancer; immune checkpoint inhibitor; urothelial carcinoma.

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Conflict of interest statement

J.S.C. and S.T.N. are co-founders of Majestic Therapeutics, LLC. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
NMIBC vs. MIBC. Not included in this figure is stage 4 bladder cancer, in which the cancer metastasizes to the lymph nodes and distal organs [5]. Illustration created with BioRender.com (accessed on 30 November 2023).
Figure 2
Figure 2
Interactions between different cells in the tumor microenvironment of UC. The green arrow represents promotion and the red arrow represents inhibition. Illustration created with BioRender.com (accessed on 30 November 2023).
Figure 3
Figure 3
Mediators of PD-L1 transcription in UC. Included are the different pathways by which PD-L1 expression is upregulated both in tumor cells and antigen-presenting cells. Illustration created with BioRender.com (accessed on 30 November 2023).
See this image and copyright information in PMC

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