美国贝勒医学院Xiang H.-F. Zhang团队近期取得重要工作进展。他们研究提出了实体瘤诱导的全身免疫抑制涉及骨髓和B细胞的二元相互作用。相关研究成果2024年9月12日在线发表于《自然—细胞生物学》杂志上。

据介绍，实体瘤诱导全身免疫抑制，涉及骨髓细胞和T细胞。B细胞相关机制的研究仍然相对不足。

研究人员发现了两种不同的肿瘤诱导的B细胞异常模式（TiBA；TiBA-1和TiBA-2），两者都与骨髓中的异常骨髓生成有关。TiBA-1可能是由于前祖细胞B细胞和髓系祖细胞之间的生态位竞争，导致下游B细胞的整体减少。TiBA-2的特征是与过量中性粒细胞相互作用驱动的独特早期B细胞群的系统性积累。

重要的是，与TiBA-2相关的早期B细胞促进衰竭样T细胞的系统性积累。来自癌症三阴性乳腺癌患者外周血的髓细胞和B细胞概括了TiBA亚型，不同的TiBA特征与标准护理免疫疗法的病理学完全反应相关。

总之，这一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细胞和髓细胞异常进行治疗的必要性。

附：英文原文

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

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

Issue&Volume: 2024-09-12

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.

DOI: 10.1038/s41556-024-01508-6

Source: https://www.nature.com/articles/s41556-024-01508-6