The Mechanism of Antitumor Immunity Induced by BCG Therapy for Bladder Cancer
Abstract
BCG immunotherapy for bladder cancer is the only bacterial cancer therapy approved for clinical use. Although presumed to induce T cell-mediated immunity, whether tumor elimination depends on bacteria-specific or tumor-specific immunity was unknown. We recently showed that BCG-induced bladder tumor elimination requires CD4 and CD8 T cells, and furthermore stimulates long-term tumor-specific immunity that primarily depends on the CD4 T cell compartment. Herein, we use our newly developed transgenic model of bladder cancer to explore the anti-tumor T cell response further, and demonstrate that BCG therapy results in enhanced activation and effector function of tumor-specific CD4 T cells, mainly through enhanced production of interferon gamma (IFNg). Accordingly, we show that BCG-induced tumor elimination and tumor-specific immune memory require tumor cell expression of the interferon gamma receptor (IFNGR), but not MHC Class II. Our findings establish that a bacterial immunotherapy for cancer is capable of inducing tumor immunity, an anti-tumor effect that results from enhanced function of tumor-specific CD4 T cells, and ultimately requires tumor-intrinsic IFNg signaling, via a mechanism that is distinct from other tumor immunotherapies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2020
- Accession Number
- AD1110819
Entities
People
- Anthony C Antonelli
Organizations
- Weill Cornell Medicine