Pan-cancer single-cell dissection reveals phenotypically distinct B cell subtypes.

Area of Science:

• Immunology
• Oncology
• Bioinformatics

Background:

• Tumor-infiltrating B cells (TIBs) play a complex role in cancer development.
• Understanding TIB heterogeneity is crucial for cancer research and therapy.

Purpose of the Study:

• To create a comprehensive resource of human B cells from diverse cancer types.
• To characterize TIB heterogeneity and identify novel tumor-enriched subpopulations.
• To assess the prognostic and predictive potential of identified TIB subsets.

Main Methods:

• Integration of single-cell RNA sequencing data from 649 cancer patients.
• Analysis of B cell abundance, subtype composition, and isotype distribution.
• Identification and characterization of tumor-enriched B cell subpopulations.

Main Results:

• Substantial heterogeneity in TIB abundance and composition was observed across 19 cancer types.
• Immunoglobulin G (IgG)-skewness in antibody-secreting cell isotypes was noted.
• Two novel tumor-enriched subpopulations, stress-response memory B cells and tumor-associated atypical B cells (TAABs), were identified.
• TAABs exhibit high clonal expansion, proliferative capacity, and interaction with CD4 T cells, predicting immunotherapy response.

Conclusions:

• This study provides a valuable resource for understanding B cell diversity in cancer.
• Identified TIB subsets, particularly TAABs, have significant prognostic and predictive value.
• Findings lay the groundwork for further exploration of B cell functions in oncology.