研究人员表示，细胞毒性T淋巴细胞（CTL）和自然杀伤细胞通过极化释放穿孔素和颗粒酶来杀死病毒感染和肿瘤细胞。穿孔素是一种成孔毒素，在目标细胞的质膜上形成一个病变，颗粒酶通过该病变进入细胞膜并启动细胞凋亡。运输所需的内体分选复合物（ESCRT）蛋白参与修复小的膜创伤。
研究人员发现，ESCRT蛋白在穿孔蛋白释放后立即在靶细胞中被精确地招募到CTL参与的部位。抑制癌源性细胞中的ESCRT机制增强了它们对CTL介导的杀伤的敏感性。因此，ESCRT机制对穿孔蛋白孔的修复限制了颗粒酶进入细胞膜，有可能使目标细胞抵御细胞溶解攻击。
附：英文原文
Title: ESCRT-mediated membrane repair protects tumor-derived cells against T cell attack
Author: Alex T. Ritter, Gleb Shtengel, C. Shan Xu, Aubrey Weigel, David P. Hoffman, Melanie Freeman, Nirmala Iyer, Nensi Alivodej, David Ackerman, Ilia Voskoboinik, Joseph Trapani, Harald F. Hess, Ira Mellman
Issue&Volume: 2022-04-22
Abstract: Cytotoxic T lymphocytes (CTLs) and natural killer cells kill virus-infected and tumor cells through the polarized release of perforin and granzymes. Perforin is a pore-forming toxin that creates a lesion in the plasma membrane of the target cell through which granzymes enter the cytosol and initiate apoptosis. Endosomal sorting complexes required for transport (ESCRT) proteins are involved in the repair of small membrane wounds. We found that ESCRT proteins were precisely recruited in target cells to sites of CTL engagement immediately after perforin release. Inhibition of ESCRT machinery in cancer-derived cells enhanced their susceptibility to CTL-mediated killing. Thus, repair of perforin pores by ESCRT machinery limits granzyme entry into the cytosol, potentially enabling target cells to resist cytolytic attack.
DOI: abl3855
Source: https://www.science.org/doi/10.1126/science.abl3855