免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
过继转移的 Th17 细胞与宿主 B 细胞协同作用，实现持久的肿瘤免疫
英文原题：Adoptively transferred Th17 cells cooperate with host B cells to achieve durable tumor immunity.
查看英文原题
Adoptively transferred Th17 cells cooperate with host B cells to achieve durable tumor immunity.
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中文摘要
CD4+ T辅助细胞在过继性T细胞治疗（ACT）的成功中发挥重要作用，但目前尚不清楚哪个亚群最具治疗潜力以及它们如何清除肿瘤。我们发现，肿瘤特异性Th17细胞比其他CD4+亚群更有效地根除黑色素瘤，并通过独特地协调宿主免疫来防止远处转移。供体Th17细胞需要宿主B细胞——而非T细胞——才能实现肿瘤消退。Th17细胞诱导B细胞增殖、活化和分化，而B细胞通过增强IL-21产生来增强Th17细胞的多功能性。Th17细胞和B细胞在淋巴组织中共定位，在那里Th17细胞通过IL-21产生和CD40L共刺激诱导生发中心和肿瘤反应性抗体。此外，这些肿瘤特异性抗体对肿瘤攻击提供部分保护。在此，我们揭示过继转移的Th17细胞与B细胞协同驱动持久免疫，证明内源性B细胞反应在有效CD4+ ACT中的作用。
展开英文摘要原文
CD4 + T helper cells play an important role in adoptive T cell therapy (ACT) success, but it remains unclear which subset is most therapeutic and how they eliminate tumors.
We find that tumor-specific Th17 cells eradicate melanoma more effectively than other CD4 + subsets and protect against distant metastases by unique orchestration of host immunity. Donor Th17 cells require host B cells -but not T cells- for tumor regression.
Th17 cells induce B cell proliferation, activation, and differentiation, while B cells augment Th17 cell polyfunctionality by enhancing IL-21 production. Th17 and B cells colocalize in lymphoid tissues, where Th17 cells induce germinal centers and tumor-reactive antibodies via IL-21 production and CD40L costimulation.
Furthermore, these tumor-specific antibodies provide partial protection against tumor challenge.
Herein, we reveal that adoptively transferred Th17 cells cooperate with B cells to drive sustained immunity, demonstrating a role for endogenous B cell responses in effective CD4 + ACT.
论文信息
- 作者
- Cole AC、Knochelmann HM、Wyatt MM、Wittling MC、Horvat NK、Smith AS、Rangel Rivera GO、Rivera Reyes AM
- 第一作者单位
- Department of Surgery, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA. Electronic address: anna.cole@emory.edu.United States
- 通讯作者单位
- Department of Surgery, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA. Electronic address: cpaulos@emory.edu.United States
- 期刊
- Cancer cell2025 Sep 8
- 原文标识
- PubMed 40712565 · DOI 10.1016/j.ccell.2025.07.001
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