They previously have shown that there are intrinsic subtypes of bladder cancer, with the basal subtype characterized by high levels of immune infiltration, and the luminal subtype characterized by immune exclusion. They found treatment with the current standard of care chemotherapeutic agents has a subtype-specific effect on the tumor microenvironment and that different chemotherapeutic regimens alter the immune microenvironment differently. Cisplatin-based chemotherapeutic treatment of luminal tumors induces a mesenchymal phenotype and immune infiltration. Two of the most widely used standard of care chemotherapeutic regiments are Cisplatin-Gemcitabine (GemCis) and Methotrexate-Vinblastine-Doxorubicin-Cisplatin (MVAC), and they showed that MVAC treatment induces significant immune infiltration within the luminal subtype while GemCis treatment does not, indicating there are treatment specific effects on the immune microenvironment. Furthermore, using subtype-specific mouse models of bladder cancer previously developed by their lab, they found GemCis and MVAC had differing effects on the immune microenvironment. They noticed epithelial plasticity due to methotrexate and not folate depletion further supporting their findings. These results indicate that differing chemotherapeutic regimens have differential effects on the tumor microenvironment which could potentially be used to increase the efficacy of immune checkpoint inhibitors. Further research is conducted to understand combination therapies and sequencing of immunotherapy following particular chemotherapy type underway.
Presented by: William Y. Kim, MD The University of North Carolina at Chapel Hill, North Carolina
Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 16th Annual Meeting of the International Bladder Cancer Network (IBCN) October 11-13, 2018 - the Inntel Hotels Rotterdam Centre, Rotterdam, The Netherlands