IBCN 2018: The Impact of Chemotherapy on Immune Microenvironment

Rotterdam, The Netherlands (UroToday.com) William Y. Kim, MD presented work he took part in on the impact of chemotherapy on the immune microenvironment. In patients with bladder cancer, programmed death-ligand-1 (PD-L1) and programmed death-1 (PD-1) inhibitors have been shown to be effective in approximately 20% patients, with preliminary findings suggesting a level of immune infiltration and immune suppression within the tumor microenvironment correlates with response to these treatments.

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