Chung, Charlie, Ozcelik, Elif, Habel, Jill, Zhang, Jialin, Qin, Yihan, Garcia, Libia, Merrill, Joseph, Chung, Taemoon, Lyons, Scott, Shen, Zeli, Fox, James G, Westcott, Peter, Beyaz, Semir (2023) Microbial regulation of anti-tumor immunity in colorectal cancer. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024, 2024 Apr 5-10, San Diego, CA.
Abstract
Colorectal cancer (CRC) is the 3rd leading site of cancers and cause of cancer cell death. Although Immunotherapies revolutionized cancer therapy, the majority of CRC patients, particularly with metastatic disease, do not respond to the treatments. This necessitates a better mechanistic understanding of the tumor-immune cell interactions in the context of CRC. Microbiome influences multiple biological aspects of the host including immune responses against cancers. Here, we show that the gut microbiome influences cancer MHC-I and -II expression levels and restricts tumor progression and metastasis, resulting in longer survival in 3 different CRC models and two different mouse strains. We found that the anti-tumor effects are dependent on T cells and B cells. Interestingly, depletion of B cell negated anti-metastatic effects of gut microbiome. Mechanistically, MHC-II expression in cancer cells mediates the anti-tumor effects of the microbiome. MHC-II upregulation on human CRC organoids enhances cancer-immune cell interactions and associated apoptosis, demonstrating an anti-tumor role and significance of MHC-II in human CRC. Thus, gut microbes that enhance MHC-II antigen presentation promotes anti-tumor immunity and may be utilized to enhance efficacy of immunotherapy in metastatic CRC.
| Item Type: | Conference or Workshop Item (Paper) |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > cancer types > intestinal cancer diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL labs > Beyaz lab CSHL labs > Lyons lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 2023 |
| Date Deposited: | 13 Aug 2024 12:55 |
| Last Modified: | 13 Aug 2024 12:55 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41633 |
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