Abstract 1408: Increased infiltrating class-switched memory B cell in breast cancer tumors were associated with favorable prognostic outcome

Abstract

Abstract Introduction: Tumor infiltrating lymphocytes are well known as an important component in the microenvironment in human cancers, including breast cancer tumors. Not only tumor infiltrating T cells, but B cells have been recognized as a new hallmark of cancer immunity. However, the roles of each B cell subset remain unclear. We investigated the breast cancer biology from the point of view of tumor infiltrating B cells. Methods: Genomic for primary breast tumors and clinical data were obtained from The Cancer Genome Atlas in Pan-Cancer Atlas publications. Fraction for 64 immune and stroma cell subsets, such as memory- and class-switched memory B cells and CD4+ memory T cell were quantified by xCell method, a performs cell type enrichment analysis from bulk tumor gene expression data. Individual tumors were dichotomized according to each cell fraction levels by median cut-off value. B receptor repertoire (BCR) recognizing specific receptor molecules on several cancer cells, were quantified from complementarity determining region (CDR) 3 sequences in the variable chains in immunoglobulins by TRUST method. Gene set enrichment analysis were demonstrated using Hallmark gene-sets. Results: CD4+ memory T cell was the dominant lymphocyte subsets (40.7%) followed by Th1 cells (22.8%) and class-switched memory B cell (3.4%). Patients with higher B cell infiltrating tumor were associated with improved disease-free survival (HR = 0.56, p = 0.01). Moreover, class-switched memory B cell was found to be the most significant prognostic factor (disease-free survival; HR = 0.23, p = 0.095, overall survival; HR = 0.33, p = 0.046). On the other hand, pro-, memory-B cells were not significant for disease outcome. Gene sets related to cell proliferation like mitotic spindle and G2M checkpoint were rather down regulated in tumors with high class-switched memory B cell infiltration compared to those with low (enrichment score = -1.63 and -1.71, p = 0.04 and 0.03, respectively). The number of unique CDR3 in breast cancer tumor has positive correlation with BCR index (Spearman r = 0.63, P <0.01), and higher class-switched memory B cell infiltrated tumors were associated with more unique CDR3s, also BCR index (P <0.01 and P <0.01, respectively). Conclusion: We found that increased infiltrating class-switched memory B cell in breast cancer associates with down-regulated cancer cell proliferation with favorable outcome. The heightened diversity of the B cell receptor caused by genome rearrangement in complementarity determining region also associated with class-switched memory B cell infiltration into breast cancer tumors. Citation Format: Mariko Asaoka, Rongrong Wu, Takashi Ishikawa. Increased infiltrating class-switched memory B cell in breast cancer tumors were associated with favorable prognostic outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1408.