近日，美国纪念斯隆凯特林癌症研究所Andrea Schietinger等研究人员合作发现，免疫疗法介导的实体瘤消除需要瘤内免疫三联体。这一研究成果发表在2024年6月20日出版的国际学术期刊《癌细胞》上。

研究人员揭示了能否利用肿瘤特异性CD4⁺ T细胞来克服肿瘤内CD8⁺ T细胞的功能障碍。研究人员发现，CD8⁺和CD4⁺ T细胞的空间定位和相互作用，而不是它们的数量，决定了采用T细胞疗法和免疫检查点阻断（ICB）时的抗肿瘤反应： 在效应阶段，CD4⁺ T细胞必须与同一树突状细胞上的CD8⁺ T细胞接触，形成三细胞型细胞簇（三联体），才能发挥CD8⁺ T细胞的细胞毒性并消灭癌细胞。

当瘤内三联体形成被破坏时，尽管肿瘤特异性CD8⁺和CD4⁺ T细胞的数量相等，肿瘤仍会发展。在接受ICB治疗的胸膜间皮瘤患者中，三联体与临床反应相关。因此，CD4⁺ T细胞和三联体是CD8⁺ T细胞在效应期发挥细胞毒性和消除肿瘤所需的。

研究人员表示，肿瘤特异性CD8⁺ T细胞经常功能失调，无法阻止肿瘤生长。

附：英文原文

Title: Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors

Author: Gabriel Espinosa-Carrasco, Edison Chiu, Aurora Scrivo, Paul Zumbo, Asim Dave, Doron Betel, Sung Wook Kang, Hee-Jin Jang, Matthew D. Hellmann, Bryan M. Burt, Hyun-Sung Lee, Andrea Schietinger

Issue&Volume: 2024-06-20

Abstract: Tumor-specific CD8+ T cells are frequently dysfunctional and unable to halt tumor growth. We investigatedwhether tumor-specific CD4+ T cells can be enlisted to overcome CD8+ T cell dysfunction within tumors. We find that the spatial positioning and interactionsof CD8+ and CD4+ T cells, but not their numbers, dictate anti-tumor responses in the context of adoptiveT cell therapy as well as immune checkpoint blockade (ICB): CD4+ T cells must engage with CD8+ T cells on the same dendritic cell during the effector phase, forming a three-cell-typecluster (triad) to license CD8+ T cell cytotoxicity and cancer cell elimination. When intratumoral triad formationis disrupted, tumors progress despite equal numbers of tumor-specific CD8+ and CD4+ T cells. In patients with pleural mesothelioma treated with ICB, triads are associatedwith clinical responses. Thus, CD4+ T cells and triads are required for CD8+ T cell cytotoxicity during the effector phase and tumor elimination.

DOI: 10.1016/j.ccell.2024.05.025

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00193-4