人类神经胶质瘤使用异柠檬酸脱氢酶 (IDH) 状态作为预测因子进行分类；然而，遗传差异和治疗效果对随后免疫的影响仍不清楚。在这项研究中，我们对 144,678 个免疫细胞使用了连续单细胞转录组学，并对包含 48 个人类神经胶质瘤的超过 200 万个免疫细胞使用了光谱细胞术，以破译它们的免疫景观。 22 种不同的免疫细胞类型有助于神经胶质瘤免疫。具体而言，在神经胶质瘤复发期间，大脑驻留小胶质细胞（MG）减少，CD8 T 淋巴细胞随之增加，与 IDH 状态无关。相反，观察到 IDH 野生型相关模式，例如大量的抗原呈递细胞样 MG 和细胞毒性 CD8 T 细胞。除了阐明 IDH、复发和治疗相关免疫方面的差异之外，我们还发现了表达颗粒溶素（一种细胞毒性肽）的新型炎症 MG 亚群，否则颗粒溶素仅在淋巴细胞中表达。此外，我们提供了一个强大的基因组框架，用于定义超越 M1/M2 范式的巨噬细胞极化，以及神经胶质瘤特异性肿瘤免疫微环境（称为 Glio-TIME-36）的参考特征，用于解卷积转录组数据集。这项研究提供了人类泛细胞的先进光学神经胶质瘤免疫背景作为转化和临床应用的宝贵指南。© 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

Human gliomas are classified using isocitrate dehydrogenase (IDH) status as a prognosticator; however, the influence of genetic differences and treatment effects on ensuing immunity remains unclear.In this study, we used sequential single-cell transcriptomics on 144,678 and spectral cytometry on over two million immune cells encompassing 48 human gliomas to decipher their immune landscape.We identified 22 distinct immune cell types that contribute to glioma immunity. Specifically, brain-resident microglia (MG) were reduced with a concomitant increase in CD8+ T lymphocytes during glioma recurrence independent of IDH status. In contrast, IDH-wild-type-associated patterns, such as an abundance of antigen-presenting cell-like MG and cytotoxic CD8+ T cells, were observed. Beyond elucidating the differences in IDH, relapse, and treatment-associated immunity, we discovered novel inflammatory MG subpopulations expressing granulysin, a cytotoxic peptide, which is otherwise expressed in lymphocytes only. Furthermore, we provide a robust genomic framework for defining macrophage polarization beyond M1/M2 paradigm and reference signatures of glioma-specific tumor immune microenvironment (termed Glio-TIME-36) for deconvoluting transcriptomic datasets.This study provides advanced optics of the human pan-glioma immune contexture as a valuable guide for translational and clinical applications.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.