Cooper Medical School of Rowan University, Camden, NJ, 08103, USA.
Department of Neurology, Cooper University Health Care, Camden, NJ, USA.
Sci Rep. 2023 Nov 27;13(1):20874. doi: 10.1038/s41598-023-48116-2.
Glioblastoma (GBM) is an aggressive primary CNS malignancy and clinical outcomes have remained stagnant despite introduction of new treatments. Understanding the tumor microenvironment (TME) in which tumor associated macrophages (TAMs) interact with T cells has been of great interest. Although previous studies examining TAMs in GBM have shown that certain TAMs are associated with specific clinical and/or pathologic features, these studies used an outdated M1/M2 paradigm of macrophage polarization and failed to include the continuum of TAM states in GBM. Perhaps most significantly, the interactions of TAMs with T cells have yet to be fully explored. Our study uses single-cell RNA sequencing data from adult IDH-wildtype GBM, with the primary aim of deciphering the cellular interactions of the 7 TAM subtypes with T cells in the GBM TME. Furthermore, the interactions discovered herein are compared to IDH-mutant astrocytoma, allowing for focus on the cellular ecosystem unique to GBM. The resulting ligand-receptor interactions, signaling sources, and global communication patterns discovered provide a framework for future studies to explore methods of leveraging the immune system for treating GBM.
胶质母细胞瘤（GBM）是一种侵袭性的中枢神经系统原发性恶性肿瘤，尽管引入了新的治疗方法，但临床结果仍停滞不前。了解肿瘤相关巨噬细胞（TAMs）与 T 细胞相互作用的肿瘤微环境（TME）一直是人们极大的兴趣所在。尽管先前研究 GBM 中的 TAMs 表明某些 TAMs 与特定的临床和/或病理特征相关，但这些研究使用了过时的巨噬细胞极化 M1/M2 范式，并且未能包括 GBM 中 TAM 状态的连续体。也许最重要的是，TAMs 与 T 细胞的相互作用尚未得到充分探索。我们的研究使用来自成人 IDH 野生型 GBM 的单细胞 RNA 测序数据，主要目的是破译 7 种 TAM 亚型与 GBM TME 中的 T 细胞的细胞相互作用。此外，本文中发现的相互作用与 IDH 突变星形细胞瘤进行了比较，从而可以专注于 GBM 特有的细胞生态系统。发现的配体-受体相互作用、信号源和全局通信模式为未来的研究提供了一个框架，以探索利用免疫系统治疗 GBM 的方法。
