实体肿瘤引起的系统性免疫抑制涉及二分法的髓系-B细胞相互作用

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

NATURE CELL BIOLOGY

影响因子:19.1

分区:生物学1区 Top / 细胞生物学1区

发表日期:2024 Nov

作者: Xiaoxin Hao, Yichao Shen, Jun Liu, Angela Alexander, Ling Wu, Zhan Xu, Liqun Yu, Yang Gao, Fengshuo Liu, Hilda L Chan, Che-Hsing Li, Yunfeng Ding, Weijie Zhang, David G Edwards, Nan Chen, Azadeh Nasrazadani, Naoto T Ueno, Bora Lim, Xiang H-F Zhang

DOI: 10.1038/s41556-024-01508-6

摘要

实体肿瘤引起的系统性免疫抑制涉及髓系细胞和T细胞，但B细胞相关机制尚未得到充分研究。本研究发现两种不同的肿瘤诱导B细胞异常（TiBA；TiBA-1和TiBA-2），都与骨髓中异常的髓系造血相关。TiBA-1可能由前祖髓系B细胞与髓系祖细胞之间的生态位竞争引起，导致下游B细胞的整体减少。TiBA-2表现为系统性积累一种独特的早期B细胞群，主要由与过多中性粒细胞的相互作用驱动。重要的是，TiBA-2相关的早期B细胞促进了系统性耗竭样T细胞的积累。来自三阴性乳腺癌患者外周血的髓系和B细胞重现了TiBA的不同亚型，这些不同的TiBA特征与标准免疫治疗的完全临床反应相关。该研究强调了肿瘤诱导的系统性变化的患者间差异，并强调了针对不同B细胞和髓系异常的个性化治疗需求。

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.