埃默里大学Chrystal M. Paulos课题组近日取得一项新成果。经过不懈努力，他们报道了过继转移的Th17细胞与宿主B细胞合作，实现持久的肿瘤免疫。2025年7月24日，国际知名学术期刊《癌细胞》发表了这一成果。

该研究团队发现肿瘤特异性Th17细胞比其他CD4⁺亚群更有效地根除黑色素瘤，并通过独特的宿主免疫协调来防止远处转移。供体Th17细胞需要宿主B细胞（而不是T细胞）才能使肿瘤消退。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的产生来增强Th17细胞的多功能性。Th17和B细胞共定位于淋巴组织，Th17细胞通过IL-21的产生和CD40L的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。

在这里，该研究团队揭示了过继性转移的Th17细胞与B细胞合作驱动持续免疫，证明了内源性B细胞应答在有效的CD4⁺ ACT中的作用。

据介绍，CD4⁺ T辅助细胞在过继T细胞治疗（ACT）的成功中起着重要作用，但目前尚不清楚哪一种亚群最具治疗性以及它们如何消除肿瘤。

附：英文原文

Title: Adoptively transferred Th17 cells cooperate with host B cells to achieve durable tumor immunity

Author: Anna C. Cole, Hannah M. Knochelmann, Megan M. Wyatt, Megen C. Wittling, Natalie K. Horvat, Aubrey S. Smith, Guillermo O. Rangel Rivera, Amalia M. Rivera Reyes, Bhavana Pavuluri, Soundharya Kumaresan, Pawel Muranski, Ayana T. Ruffin, Jeremy M. Boss, Gregory B. Lesinski, Chrystal M. Paulos

Issue&Volume: 2025-07-24

Abstract: 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.

DOI: 10.1016/j.ccell.2025.07.001

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00272-7