嗜金属边缘区巨噬细胞穿过CD8⁺ T细胞介导的针对血源性肿瘤的保护性免疫，这一成果由巴黎大学Peter van Endert研究组经过不懈努力而取得。相关论文于2025年3月25日发表在《免疫学》杂志上。

研究小组开发了一种纯化方案，使MMMs的表型和转录特性。MMMs基因表达谱富集了与CD8⁺ T细胞活化和主要组织相容性复合体I类（MHC I类）交叉呈现相关的途径。在体外，纯化的MMMs与传统的1型树突状细胞（cDC1s）在CD8⁺ T细胞中交叉引发可溶性和颗粒性抗原，但MMMs采用不同的空泡加工途径。体内双光子和离体光片成像显示与同源T细胞分化为效应器的长期接触。MMMs通过捕获血源性肿瘤抗原和将肿瘤细胞注入脾脏，交叉启动保护性CD8⁺ T细胞抗肿瘤反应。这种交叉引物需要MMMs表达转录因子Batf3，但不依赖于cDC1s介导的肿瘤物质的交叉呈递或MHC I类修饰。因此，MMMs将控制血源性病原体和肿瘤物质的传播与先天和适应性反应的启动结合起来。

据了解，脾亲金属边缘区巨噬细胞（MMMs）被定位为控制血源性威胁的传播。

附：英文原文

Title: Metallophilic marginal zone macrophages cross-prime CD8+ T cell-mediated protective immunity against blood-borne tumors

Author: Franois-Xavier Mauvais, Yamina Hamel, Aymeric Silvin, Kevin Mulder, Kai Hildner, Ramazan Akyol, Marc Dalod, Despoina Koumantou, Loredana Saveanu, Meriem Garfa, Nicolas Cagnard, Barbara Bertocci, Florent Ginhoux, Peter van Endert

Issue&Volume: 2025-03-25

Abstract: Splenic metallophilic marginal zone macrophages (MMMs) are positioned to control the dissemination of blood-borne threats. We developed a purification protocol to enable characterization of MMMs phenotypically and transcriptionally. MMM gene expression profile was enriched for pathways associated with CD8+ T cell activation and major histocompatibility complex class I (MHC class I) cross-presentation. In vitro, purified MMMs equaled conventional dendritic cells type 1 (cDC1s) in cross-priming CD8+ T cells to soluble and particulate antigens, yet MMMs employed a distinct vacuolar processing pathway. In vivo biphoton and ex vivo light-sheet imaging showed long-standing contacts with cognate T cells differentiating to effectors. MMMs cross-primed protective CD8+ T cell antitumor responses both by capturing blood-borne tumor antigens and by internalizing tumor cells seeding the spleen. This cross-priming required expression of the transcription factor Batf3 by MMMs but was independent of cDC1-mediated capture of tumor material for cross-presentation or MHC class I-dressing. Thus, MMMs combine control of the dissemination of blood-borne pathogens and tumor materials with the initiation of innate and adaptive responses.

DOI: 10.1016/j.immuni.2025.02.027

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00094-9