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. 2024 Nov;26(11):1971-1983.
doi: 10.1038/s41556-024-01508-6. Epub 2024 Sep 12.

Solid tumour-induced systemic immunosuppression involves dichotomous myeloid-B cell interactions

Xiaoxin Hao #  1   2   3   4 , Yichao Shen #  1   2   4   5   6 , Jun Liu  1   2   5 , Angela Alexander  7 , Ling Wu  1   2   5 , Zhan Xu  1   2   5 , Liqun Yu  1   2   5 , Yang Gao  1   2   5 , Fengshuo Liu  1   2   5   8 , Hilda L Chan  1   2   5   9 , Che-Hsing Li  10 , Yunfeng Ding  1   2   5 , Weijie Zhang  11   12 , David G Edwards  1   2   5 , Nan Chen  1   2 , Azadeh Nasrazadani  7 , Naoto T Ueno  7   13 , Bora Lim  1   2   5 , Xiang H-F Zhang  14   15   16   17
Affiliations

Solid tumour-induced systemic immunosuppression involves dichotomous myeloid-B cell interactions

Xiaoxin Hao et al. Nat Cell Biol. 2024 Nov.

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.

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Conflict of interest statement

Competing interests The authors declare no competing interests.

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