Lei, Pin-Ji, Pereira, Ethel, Andersson, Patrik, Amoozgar, Zohreh, Van Wijnbergen, Jan Willem, O'Melia, Meghan J, Zhou, Hengbo, Chatterjee, Sampurna, Ho, William Wee, Posada, Jessica M, Kumar, Ashwin Srinivasan, Morita, Satoru, Chuang, Charlie, Ergin, Ilgin, Jones, Dennis, Huang, Peigen, Beyaz, Semir, Padera, Timothy P (2023) Single cell analysis of breast cancer progression and metastasis to lymph nodes reveals cancer cell plasticity and MHC class II-mediated immune regulation. In: 114th Annual Meeting of the American Association for Cancer Research (AACR), APR 14-19, 2023, Orlando, FL.
Abstract
Tumor-draining lymph nodes are critical sites for generating tumor antigen-specific T cells and are associated with durable immune responses. However, lymph nodes are often the first site of metastasis and lymph node metastases portend worse outcomes. Through cross species single cell gene expression analysis of breast cancer progression and metastasis to lymph nodes, we uncovered features that define the heterogeneity, plasticity, and immune evasion of cancer cells. Notably, a subpopulation of metastatic cancer cells in the lymph node were marked by high levels of MHC class II (MHC-II) gene expression both in mice and humans. Mechanistically, the IFN-γ and JAK/STAT signaling pathways mediate MHC-II expression in cancer cells. Ablation of IFNGR1/2 or CIITA, the transactivator of MHC-II, in cancer cells prevented tumor progression. Interestingly, MHC-II+ cancer cells lacked co-stimulatory molecule expression, engendered the expansion of regulatory T cells and blunted CD4+ effector T cells in the tumor draining lymph nodes and favor tumor progression. Overall, our data suggests that cancer cell plasticity during breast cancer progression and metastasis to lymph nodes endows metastatic cells with the ability to avoid immune surveillance. These data provide the basis for new opportunities to therapeutically stimulate anti-cancer immune responses against local and systemic metastases.
| Item Type: | Conference or Workshop Item (Poster) |
|---|---|
| Subjects: | diseases & disorders > cancer > cancer types > breast cancer diseases & disorders > cancer > metastasis |
| CSHL Authors: | |
| Communities: | CSHL labs > Beyaz lab CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 2023 |
| Date Deposited: | 19 Sep 2023 18:43 |
| Last Modified: | 30 Apr 2024 18:45 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/40920 |
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