Tissue-resident FOLR2⁺ macrophages associate with CD8⁺ T cell infiltration in human breast cancer.

IF 5.5 1区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Chemical Theory and Computation Pub Date : 2022-03-31 Epub Date: 2022-03-23 DOI:10.1016/j.cell.2022.02.021

Rodrigo Nalio Ramos, Yoann Missolo-Koussou, Yohan Gerber-Ferder, Christian P Bromley, Mattia Bugatti, Nicolas Gonzalo Núñez, Jimena Tosello Boari, Wilfrid Richer, Laurie Menger, Jordan Denizeau, Christine Sedlik, Pamela Caudana, Fiorella Kotsias, Leticia L Niborski, Sophie Viel, Mylène Bohec, Sonia Lameiras, Sylvain Baulande, Laëtitia Lesage, André Nicolas, Didier Meseure, Anne Vincent-Salomon, Fabien Reyal, Charles-Antoine Dutertre, Florent Ginhoux, Lene Vimeux, Emmanuel Donnadieu, Bénédicte Buttard, Jérôme Galon, Santiago Zelenay, William Vermi, Pierre Guermonprez, Eliane Piaggio, Julie Helft

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引用次数: 0

Abstract

Macrophage infiltration is a hallmark of solid cancers, and overall macrophage infiltration correlates with lower patient survival and resistance to therapy. Tumor-associated macrophages, however, are phenotypically and functionally heterogeneous. Specific subsets of tumor-associated macrophage might be endowed with distinct roles on cancer progression and antitumor immunity. Here, we identify a discrete population of FOLR2⁺ tissue-resident macrophages in healthy mammary gland and breast cancer primary tumors. FOLR2⁺ macrophages localize in perivascular areas in the tumor stroma, where they interact with CD8⁺ T cells. FOLR2⁺ macrophages efficiently prime effector CD8⁺ T cells ex vivo. The density of FOLR2⁺ macrophages in tumors positively correlates with better patient survival. This study highlights specific roles for tumor-associated macrophage subsets and paves the way for subset-targeted therapeutic interventions in macrophages-based cancer therapies.

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组织驻留的 FOLR2+ 巨噬细胞与人类乳腺癌的 CD8+ T 细胞浸润有关。

巨噬细胞浸润是实体瘤的特征之一，巨噬细胞的整体浸润与患者生存率降低和耐药性有关。然而，肿瘤相关巨噬细胞在表型和功能上具有异质性。肿瘤相关巨噬细胞的特定亚群可能在癌症进展和抗肿瘤免疫方面具有不同的作用。在这里，我们在健康乳腺和乳腺癌原发肿瘤中发现了一个离散的 FOLR2+ 组织驻留巨噬细胞群体。FOLR2+ 巨噬细胞定位于肿瘤基质的血管周围区域，它们在那里与 CD8+ T 细胞相互作用。FOLR2+ 巨噬细胞在体内能有效地激发效应 CD8+ T 细胞。肿瘤中 FOLR2+ 巨噬细胞的密度与患者的生存率成正相关。这项研究强调了肿瘤相关巨噬细胞亚群的特殊作用，并为基于巨噬细胞的癌症疗法中的亚群靶向治疗干预铺平了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Chemical Theory and Computation 化学-物理：原子、分子和化学物理

CiteScore

9.90

自引率

16.40%

发文量

568

审稿时长

1 months

期刊介绍： The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.