The Role Of B Cell Specific MHC II Antigen Presentation In Breast Cancer Progression And Immune Checkpoint Blockade Therapy 2310330

Abstract

Abstract Introduction Breast cancer remains the leading cause of cancer-related mortality in women. Immunotherapies have revolutionized treatment; however, their efficacy relies heavily on immune cell-mediated antigen (ag) presentation within the tumor microenvironment (TME). The often overlooked role of B cell ag presentation may be important in anti-tumor immunity. B cells are potent ag presenting cells and therole of B cell ag presentation in progression of mouse models of autoimmune diseases has been demonstrated. B cells may have a potent role in breaking immune tolerance towards self-peptides. We hypothesize that B cell specific MHC II ag presentation plays a non-redundant role in promoting anti-tumor immunity. Methods To investigate the role of B cell MHC II ag presentation in tumor progression, we generated B cell-specific MHC II knockout mice and utilized the E0771, a murine triple-negative breast cancer (TNBC), and E0771-LN26 cell line with a propensity for lymph node and metastases. Tumor growth was assessed in B cell MHC II-deficient and wild-type littermates. We also assessed tumor growth in anti-PD-1 treated condition. To understand the relevance of this study in human TNBCs, we generated co-relation of MHC II expression in breast cancer on patient outcome, we analyzed publicly available TNBC data. Results Our data demonstrate that E0771 and E0771-LN2 tumors exhibit accelerated growth in B cell-specific MHC II knockout mice compared to MHC II fl/fl controls, highlighting a critical role for B cell-mediated MHC II ag presentation in controlling tumor progression. Moreover, T cells from mice lacking B cell specific MHC II expression had were more exhausted. Intrestingly, mice lacking B cell MHC II expression were more responsive to anti-PD-1 treatment. We also found a co-relation of high MHC II expression with better patient outcome. Conclusion These findings suggest that B cell-mediated antigen presentation plays a context dependent role in modulating anti-tumor immune responses in breast cancer. Funding Source This research project is supported by funding from NCI Topic Categories Classical and Non-Classical Antigen Presenting Cells (APC)