实体瘤引起的全身免疫抑制涉及二分法髓样-B细胞相互作用
Solid tumour-induced systemic immunosuppression involves dichotomous myeloid-B cell interactions
影响因子:19.10000
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
摘要
实体瘤诱导涉及髓样细胞和T细胞的全身免疫抑制。 B细胞相关的机制仍然相对研究。在这里，我们发现了肿瘤诱导的B细胞异常的两种不同模式（TIBA； TIBA-1和TIBA-2），这两种模式都与骨髓中骨髓异常有关。 TIBA-1可能是由前生细胞和髓样祖细胞之间的利基竞争引起的，导致下游B细胞的全球减少。 TIBA-2的特征是由与过度嗜中性粒细胞相互作用的独特早期B细胞种群的全身积累。重要的是，TIBA-2相关的早期B细胞促进了疲惫的T细胞的全身积累。三阴性乳腺癌患者外周血的髓样细胞和B细胞概括了TIBA亚型，而独特的TIBA轮廓与对标准免疫疗法的病理完全反应有关。这项研究强调了肿瘤引起的全身变化的患者间多样性，并强调了针对不同B和髓样细胞异常量身定制的治疗。
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.