南京医科大学汪秀星等合作，近期取得重要工作进展。他们研究提出，浸润浆细胞通过IgG-Tumor结合维持胶质母细胞瘤干细胞。相关研究成果2025年1月2日在线发表于《癌细胞》杂志上。

据介绍，胶质母细胞瘤是一种高度侵袭性的原发性脑肿瘤，胶质母细瘤干细胞（GSC）强化了肿瘤内的层次结构。浆细胞（PC）是B系免疫系统的关键效应器，但它们在胶质母细胞瘤中的作用在很大程度上尚未得到探索。

研究人员利用肿瘤浸润的B系细胞的单细胞RNA和B细胞受体测序，发现PC在浸润B系的胶质母细胞瘤人群中异常富集，经历低水平的体细胞高突变，并与预后不良有关。PC分泌免疫球蛋白G（IgG），通过IgG FcγRIIA AKT-mTOR轴刺激GSC增殖。IgG FcγRIIA旁分泌通讯的中断抑制GSC增殖和自我更新。浸润PC的胶质母细胞瘤通过CCL2-CCR2趋化因子程序被招募到GSC生态位。GSC还通过FcγRIIA信号从广泛使用的基于单克隆抗体的免疫检查点抑制剂中获得促增殖信号。

总之，这一研究数据生成了胶质母细胞瘤中B系细胞的图谱，该图谱具有肿瘤细胞内在和微环境依赖性的组合靶向框架。

附：英文原文

Title: Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding

Author: Jiancheng Gao, Danling Gu, Kailin Yang, Junxia Zhang, Qiankun Lin, Wei Yuan, Xu Zhu, Deobrat Dixit, Ryan C. Gimple, Hao You, Qian Zhang, Zhumei Shi, Xiao Fan, Qiulian Wu, Chenfei Lu, Zhangchun Cheng, Daqi Li, Linjie Zhao, Bin Xue, Zhu Zhu, Zhe Zhu, Hui Yang, Ningwei Zhao, Wei Gao, Yingmei Lu, Junfei Shao, Chuandong Cheng, Dapeng Hao, Shuo Yang, Yun Chen, Xiaoming Wang, Chunsheng Kang, Jing Ji, Jianghong Man, Sameer Agnihotri, Qianghu Wang, Fan Lin, Xu Qian, Stephen C. Mack, Zhibin Hu, Chaojun Li, Michael D. Taylor, Yan Li, Nu Zhang, Jeremy N. Rich, Yongping You, Xiuxing Wang

Issue&Volume: 2025-01-02

Abstract: Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis. PCs secrete immunoglobulin G (IgG), which stimulates GSC proliferation via the IgG-FcγRIIA-AKT-mTOR axis. Disruption of IgG-FcγRIIA paracrine communication inhibits GSC proliferation and self-renewal. Glioblastoma-infiltrating PCs are recruited to GSC niches via CCL2-CCR2 chemokine program. GSCs further derive pro-proliferative signals from broadly utilized monoclonal antibody-based immune checkpoint inhibitors via FcγRIIA signaling. Our data generate an atlas of B-lineage cells in glioblastoma with a framework for combinatorial targeting of both tumor cell-intrinsic and microenvironmental dependencies.

DOI: 10.1016/j.ccell.2024.12.006

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00481-1