GSDMs家族蛋白介导细胞焦亡在抗肿瘤免疫中的作用

细胞焦亡是一种调节性细胞死亡方式。Gasdermine（GSDMs）是一类执行细胞焦亡的胞内蛋白质。虽然GSDMs表达后的完整蛋白质不具有活性，但能被某些蛋白水解酶激活。被激活的GSDMs N端在质膜上穿孔，导致细胞裂解，引起细胞内的促炎分子及损伤相关分子模式（danger-associated molecular patterns，DAMPs）迅速有效地从焦亡细胞中释放，从而引发炎症和免疫反应。焦亡细胞促进抗肿瘤免疫作用可能涉及细胞毒性T淋巴细胞对肿瘤细胞的杀伤。本文介绍GSDMs介导的细胞焦亡及细胞焦亡过程中引发促炎症和免疫反应的关键分子，并且探讨细胞焦亡对肿瘤治疗的有利及不利因素，以期更好地了解细胞焦亡对肿瘤免疫微环境的影响及对肿瘤免疫治疗的作用，有助于促进恶性肿瘤治疗策略的改进。

The Role of Cell Pyroptosis Mediated by GSDMs in Antitumor Immunity

Pyroptosis, a type of regulated cell death, has been shown to be immunogenic in quite a few studies. Pyroptosis has been observed since 1986 and was found to be mediated by GSDM family proteins until recently. Gasdermines (GSDMs) are a group of intracellular proteins that mediates cell pyroptosis. Although GSDMs are expressed in inactive forms, some proteolytic enzymes can activate them. The N-terminus of activated GSDMs perforate the plasma membrane, resulting in cell lysis. Pyroptosis is a double-edged sword that is closely related to the tumor immune microenvironment. Pro-inflammatory molecules and DAMPs will be quickly and effectively released into the microenvironment from the pyroptotic cells, and trigger inflammation and immune response, while these immune responses are not always positive. Inductions of pyroptotic cell death have been shown to promote anti-tumor immunity and improve the efficacy of immune checkpoint inhibitors, which involves the cytotoxic effects of effector T lymphocytes, or reprogramming of the tumor microenvironment to an immunostimulatory state. In this review, we not only summarize the mechanisms of different types of pyroptosis and the key molecules that promote inflammatory and immune response during pyroptosis, but also compare its common features with apoptosis. In addition, we discuss the potential positive and negative factors to cancer therapy during pyroptosis. Although our understanding of pyroptosis in cancer is growing, many mechanisms remain unclear: how pyroptosis activates the immune system, how pyroptosis is regulated, and how pyroptosis can be harnessed therapeutically to improve cancer immunotherapy or to reduce therapy related toxicity. We hope this review will help further understanding the role of pyroptosis in tumor microenvironment and cancer immune therapy, promoting the improvement of cancer therapy strategies.