Bacterial immunotherapy for cancer induces CD4-dependent tumor-specific immunity through tumor-intrinsic interferon-γ signaling Journal Article
| Authors: | Antonelli, A. C.; Binyamin, A.; Hohl, T. M.; Glickman, M. S.; Redelman-Sidi, G. |
| Article Title: | Bacterial immunotherapy for cancer induces CD4-dependent tumor-specific immunity through tumor-intrinsic interferon-γ signaling |
| Abstract: | Bacillus Calmette-Guérin (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 is unknown. Herein we show that BCG-induced bladder tumor elimination requires CD4 and CD8 T cells, although augmentation or inhibition of bacterial antigen-specific T cell responses does not alter the efficacy of BCG-induced tumor elimination. In contrast, BCG stimulates long-term tumor-specific immunity that primarily depends on CD4 T cells.We demonstrate that BCG therapy results in enhanced effector function of tumor-specific CD4 T cells, mainly through enhanced production of IFN-γ. Accordingly, BCGinduced tumor elimination and tumor-specific immune memory require tumor cell expression of the IFN-γ receptor, but not MHC class II. Our findings establish that a bacterial immunotherapy for cancer is capable of inducing tumor immunity, an antitumor effect that results from enhanced function of tumor-specific CD4 T cells, and ultimately requires tumor-intrinsic IFN-γ signaling, via a mechanism that is distinct from other tumor immunotherapies. © 2020 National Academy of Sciences. All rights reserved. |
| Keywords: | signal transduction; controlled study; protein expression; drug efficacy; nonhuman; cd8+ t lymphocyte; animal cell; mouse; animal tissue; bcg vaccine; cancer immunotherapy; animal experiment; animal model; cohort analysis; bladder cancer; bladder tumor; immunotherapy; gamma interferon; cd4+ t lymphocyte; tumor cell; tumor immunity; major histocompatibility complex; immunological memory; t cell; bcg; human; female; priority journal; article; disease elimination |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 117 |
| Issue: | 31 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2020-08-04 |
| Start Page: | 18627 |
| End Page: | 18637 |
| Language: | English |
| DOI: | 10.1073/pnas.2004421117 |
| PUBMED: | 32680964 |
| PROVIDER: | scopus |
| PMCID: | PMC7414065 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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