On April 12, 2021, Dr. Zhang Yu’s lab published an article entitled "Atlas of breast cancer infected B-lymphocytes reported by paired single cell RNA sequencing and anti receptor profiling" in Nature Communications. The study first comprehensively described the map of breast cancer infiltrated B cells at the single-cell level, described 13 subpopulations of breast cancer infiltrating B cells and their functions, and revealed that the infiltrated B cells in tumor may come from memory in situ by B cell receptor (BCR) sequence analysis. The B-cell signatures based on the single-cell RNA-sequencing results are significantly associated with improved survival in breast tumor patients.
Although the roles of the immune system in tumor development and therapy were proposed long ago, they have only been recognized and mechanistically investigated recently. Both the innate immune system (macrophages, neutrophils, mast cells, myeloid cells, dendritic cells, and natural killer (NK) cells) and adaptive immune system (T and B lymphocytes) contribute to the establishment of an immunosuppressive tumor microenvironment, which is one of the hallmarks of cancer.
While it is well acknowledged that T lymphocyte-mediated adaptive cellular immunity has critical functions in the immune response for tumors, the roles of B lymphocytes in tumor development and therapy, both positive and negative, have only been proposed very recently and are still mostly controversial. B cells may participate in tumor immunology through antibody production, antigen presentation, cytokine and chemokine production, and other immunoregulatory mechanisms.
To gain mechanistic insights into the functions and developmental dynamics of tumor-infiltrated immune cells, especially B-lymphocytes, here we combine single-cell RNA-sequencing and antigen receptor lineage analysis to characterize a large number of triple-negative breast cancer infiltrated immune cells and report a comprehensive atlas of tumor-infiltrated B-lymphocytes. The single-cell transcriptional profiles reveal significant heterogeneity in tumor-infiltrated B-cell subgroups. The single-cell antigen receptor analyses demonstrate that compared with those in peripheral blood, tumor-infiltrated B-cells have more mature and memory B-cell characteristics, higher clonality, more class switching recombination and somatic hypermutations. Combined analyses suggest local differentiation of infiltrated memory B-cells within breast tumors.
Figure1. a. The t-SNE projection of 8632 B cells from TNBC patients shows four major cellular clusters. b. Selected marker genes to define each B cell cluster. c. The distributions of four clusters in each patient sample. The p values were calculated by two-tailed paired Student’s t test. d. Heat maps show the distribution of the same IGH germline events (upper panel) and the same IGH sequence events (lower panel) among the four B cell clusters for TNBC and PBMC samples
The B-cell signatures based on the single-cell RNA-sequencing results are significantly associated with improved survival in breast tumor patients. Functional analyses of tumor-infiltrated B-cell populations suggest that mechanistically, B-cell subgroups may contribute to immunosurveillance through various pathways. Further dissection of tumor-infiltrated B-cell populations will provide valuable clues for tumor immunotherapy.
Figure 2. Upper panel. Kaplan–Meier
survival curves for the overall survival (left panels) and disease-free
survival (right panels) of METABRIC TNBC patients according to single gene
expression (CD20) or combined gene transcription signatures (naive B cells and
memory B cells). Lower panel. Prognostic effect of CD20, naive B signature, and
memory B signature in METABRIC TNBC patients.
Qingtao Hu and Yu Hong from Dr. Yu Zhang’s lab, and Pan Qi from Xinxiang Hospital are co-first authors of this paper. Dr. Yu Zhang is the corresponding author. Other contributing authors include Guangqing Lu, Xueying Mai, and Linlin Gao from Dr. Yu Zhang’s lab and Zhiyi Jing, Jiawen Wang, and Tao Cai in NIBS. The research in Yu Zhang’s lab is supported by National Natural Science Foundation of China (81572795, 81773304), the “Hundred, Thousand and Ten Thousand Talent Project” by Beijing municipal government (2019A39). Qingtao Hu is supported by National Natural Science Foundation of China (31701135).
Original link:
https://www.nature.com/articles/s41467-021-22300-2
