Supplementary Table from BCG-Induced Tumor Immunity Requires Tumor-Intrinsic CIITA Independent of MHC-II
Funding
CCSG
Ludwig Center for Cancer Immunotherapy
NCI
National Institute of Allergy and Infectious Disease
NIH
Department of Defense Congressionally Directed Medical Research Programs Horizon Award
ARTICLE ABSTRACT
For decades, BCG immunotherapy has been the standard of care for non–muscle-invasive bladder cancer. Despite this clinical experience, the mechanism by which BCG stimulates tumor-eliminating immunity is unclear, and there is still a need for more accurate prediction of clinical outcomes in advance of treatment initiation. We have shown that BCG stimulates tumor-specific T-cell immunity that requires tumor cell expression of the IFNγ receptor (IFNGR); however, the downstream components of IFNGR signaling responsible for responsiveness to BCG are unknown. Here, we demonstrate that the IFNγ-driven, tumor cell intrinsic expression of the class II transactivator CIITA is required for activation of a tumor-specific CD4 T-cell response and BCG-induced tumor immunity. Despite the established role for CIITA in controlling MHC-II antigen presentation machinery, the requirement for CIITA is independent of MHC-II and associated genes. Rather, we find that CIITA is required for a broader tumor-intrinsic transcriptional program linked to critical pathways of tumor immunity via mechanisms that remain to be determined. Tumor cell intrinsic expression of CIITA is not required for a response to immunotherapy targeting programmed cell death protein 1 (PD-1), suggesting that different modalities of immunotherapy for bladder cancer could be employed based on tumor-intrinsic characteristics.
