BCG-induced tumor immunity requires tumor-intrinsic CIITA independent of MHC-II Journal Article
| Authors: | Redelman-Sidi, G.; Binyamin, A.; Antonelli, A. C.; Catalano, W.; Bean, J.; Al-Ahmadie, H.; Jungbluth, A. A.; Glickman, M. S. |
| Article Title: | BCG-induced tumor immunity requires tumor-intrinsic CIITA independent of MHC-II |
| 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. ©2022 American Association for Cancer Research. |
| Keywords: | genetics; bcg vaccine; nuclear protein; bladder tumor; urinary bladder neoplasms; nuclear proteins; transactivator protein; hla antigen class 2; trans-activators; histocompatibility antigens class ii; programmed death 1 receptor; humans; human; programmed cell death 1 receptor; mhc class ii transactivator protein |
| Journal Title: | Cancer Immunology Research |
| Volume: | 10 |
| Issue: | 10 |
| ISSN: | 2326-6066 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2022-10-01 |
| Start Page: | 1241 |
| End Page: | 1253 |
| Language: | English |
| DOI: | 10.1158/2326-6066.Cir-22-0157 |
| PUBMED: | 36040405 |
| PROVIDER: | scopus |
| PMCID: | PMC9532361 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2022 -- Source: Scopus |
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