近日，英国牛津大学Tao Dong及其小组发现，非经典人类CD61与CD103配对可促进TCR信号转导和抗原特异性T细胞细胞毒性。相关论文于2024年4月1日在线发表在《自然—免疫学》杂志上。

研究人员展示了一种意想不到的瞬时CD61表达，它与CD103配对出现在T细胞的突触微簇上。CD61与T细胞抗原受体的共定位进一步调节了下游T细胞抗原受体的信号转导，提高了抗肿瘤细胞毒性，促进了对肿瘤生长的生理性控制。在临床上，CD61⁺肿瘤浸润T淋巴细胞的存在与临床预后的改善有关，其作用机制是效应功能和表型的增强，而细胞衰竭的证据有限。

总之，这项研究在人类免疫细胞上发现了一种非经典的瞬时CD61表达和与CD103的配对，这为基于免疫的细胞疗法提供了一个新的靶点。

研究人员表示，癌症仍然是导致全球死亡的主要原因之一，因此人们越来越关注利用免疫疗法策略来改善癌症治疗。在过去十年中，CD103⁺ T细胞与癌症患者更好的临床预后有关。然而，CD103介导的保护性免疫的具体免疫机制仍不清楚。

附：英文原文

Title: Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity

Author: Hamid, Megat H. B. A., Cespedes, Pablo F., Jin, Chen, Chen, Ji-Li, Gileadi, Uzi, Antoun, Elie, Liang, Zhu, Gao, Fei, Teague, Renuka, Manoharan, Nikita, Maldonado-Perez, David, Khalid-Alham, Nasullah, Cerundolo, Lucia, Ciaoca, Raul, Hester, Svenja S., Pinto-Fernndez, Adn, Draganov, Simeon D., Vendrell, Iolanda, Liu, Guihai, Yao, Xuan, Kvalvaag, Audun, Dominey-Foy, Delaney C. C., Nanayakkara, Charunya, Kanellakis, Nikolaos, Chen, Yi-Ling, Waugh, Craig, Clark, Sally-Ann, Clark, Kevin, Sopp, Paul, Rahman, Najib M., Verrill, Clare, Kessler, Benedikt M., Ogg, Graham, Fernandes, Ricardo A., Fisher, Roman, Peng, Yanchun, Dustin, Michael L., Dong, Tao

Issue&Volume: 2024-04-01

Abstract: Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.

DOI: 10.1038/s41590-024-01802-3

Source: https://www.nature.com/articles/s41590-024-01802-3