Language

English

Publication Date

11-1-2024

Journal

Nature Cell Biology

DOI

10.1038/s41556-024-01508-6

PMID

39266726

PMCID

PMC12228142

PubMedCentral® Posted Date

11-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Solid tumours induce systemic immunosuppression that involves myeloid and T cells. B cell-related mechanisms remain relatively understudied. Here we discover two distinct patterns of tumour-induced B cell abnormality (TiBA; TiBA-1 and TiBA-2), both associated with abnormal myelopoiesis in the bone marrow. TiBA-1 probably results from the niche competition between pre-progenitor-B cells and myeloid progenitors, leading to a global reduction in downstream B cells. TiBA-2 is characterized by systemic accumulation of a unique early B cell population, driven by interaction with excessive neutrophils. Importantly, TiBA-2-associated early B cells foster the systemic accumulation of exhaustion-like T cells. Myeloid and B cells from the peripheral blood of patients with triple-negative breast cancer recapitulate the TiBA subtypes, and the distinct TiBA profile correlates with pathologic complete responses to standard-of-care immunotherapy. This study underscores the inter-patient diversity of tumour-induced systemic changes and emphasizes the need for treatments tailored to different B and myeloid cell abnormalities.

Keywords

Humans, Female, Myeloid Cells, B-Lymphocytes, Immune Tolerance, Cell Communication, Triple Negative Breast Neoplasms, Myelopoiesis, Animals, Neutrophils, T-Lymphocytes, Mice, Tumor Microenvironment, Middle Aged

Published Open-Access

yes

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