PO.TB10.09 · 肿瘤生物学

乳腺癌 T 细胞状态的蛋白转录组学解析鉴定出与免疫治疗应答相关的 CD103+ Tfh 来源的细胞毒性 CD4+ 细胞

Proteotranscriptomic dissection of breast cancer T cell states identifies CD103+ Tfh-derived cytotoxic CD4+ cells linked to immunotherapy response

编号 7411 展板 28 时间 4/22 09:00–12:00 区域 Section 27 主讲 Ghamdan Al-Eryani, PhD

分会场 Functional and Spatial Regulation of Immune Evasion and Anti-Tumor Immunity

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作者与单位 Authors & Affiliations

Ghamdan Al-Eryani¹, Sophie van der Leij², Etienne Masle-Farquhar², Alma Andersson³, Kate Harvey², Sunny Wu², Tony Wang², John Reeves², Cindy Ma², Daniel L. Roden², Charles M. Perou⁴, Nir Hacohen¹, Aziz Al’Khafaji¹, Mats Nilsson⁵, Joakim Lundeberg³, Marcel Batten², Simon Junankar², Alexander Swarbrick²

¹Broad Institute, Cambridge, MA,²Garvan Institute of Medical Research, Darlinghurst, Australia,³Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden,⁴UNC Lineberger Comprehensive Cancer, Chapel Hill, NC,⁵Stockholm University, Stockholm, Sweden

摘要 Abstract

中文摘要

虽然癌症免疫治疗主要聚焦于激活细胞毒性 CD8 杀伤，但 CD4 T 细胞活性在多种癌症中也与生存和免疫治疗应答相关。我们将整合的单细胞 RNA 测序和多重蛋白表位分析应用于乳腺癌样本，以解析肿瘤微环境内免疫细胞状态的复杂性。该方法提高了表型分辨率，在滤泡辅助性 T（Tfh）细胞簇内鉴定出三种不同的状态。一种 CXCR4high 祖细胞状态产生了两种分化状态：一种为类似传统 Tfh 细胞、定位于富含 B 细胞的淋巴聚集体的 IGFL2high 亚群；另一种为 CD103+ 亚群，表现出组织驻留、耗竭和细胞毒性的特征，并与肿瘤病灶共定位。发现 CD103+ 类 Tfh 细胞通过产生 CCL 趋化因子和 CSF1 与 CXCL10+ 巨噬细胞相互作用。较高的 CD103+ Tfh 与 IGFL2high Tfh 比值与患者生存改善和对抗 PD1 检查点阻断的应答增强相关。这些发现将 Tfh 和具有细胞毒性潜能的 CD4 整合于乳腺癌中，为抗肿瘤免疫和检查点阻断应答提供了新的见解。

查看英文原文 English abstract

While cancer immunotherapies have primarily focused on activation of cytotoxic CD8 killing, CD4 T cell activity is also associated with survival and immunotherapeutic response in numerous cancers. We applied integrated single-cell RNA sequencing and multiplexed protein epitope profiling to breast cancer samples to resolve the complexity of immune cell states within the tumor microenvironment. This approach enhanced phenotypic resolution, identifying three distinct states within the T follicular helper (Tfh) cell cluster. A CXCR4high progenitor state gave rise to two differentiated states: an IGFL2high subset resembling conventional Tfh cells and localised to B cell-rich lymphoid aggregates, and a CD103+ subset, exhibiting features of tissue residency, exhaustion, and cytotoxicity, which co-localised with tumor foci. CD103+ Tfh-like cells were found to interact with CXCL10+ macrophages through production of CCL chemokines and CSF1. A higher CD103+ Tfh to IGFL2high Tfh ratio correlated with improved patient survival and enhanced responses to anti-PD1 checkpoint blockade. These findings integrate Tfh and CD4 with cytotoxic potential in breast cancer, offering new insight into anti-tumor immunity and response to checkpoint blockade.

利益披露 Disclosure

G. Al-Eryani, None.. S. van der Leij, None.. E. Masle-Farquhar, None.. A. Andersson, None.. K. Harvey, None.. T. Wang, None.. J. Reeves, None.. C. Ma, None.. D. L. Roden, None.. C. M. Perou, None.. N. Hacohen, None.. A. Al’Khafaji, None.. M. Batten, None.

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