炎症在癌症发展中起着关键作用，慢性炎症促进肿瘤进展和治疗抵抗，而急性炎症反应有助于保护性抗肿瘤免疫。 Gasdermin D (GSDMD) 介导促炎细胞因子的释放，例如 IL-1β。虽然 IL-1β 的释放与多种癌症的进展直接相关，但 GSDMD 在癌症中的作用尚不清楚。在这项研究中，我们发现 GSDMD 表达在人类乳腺癌、肾癌、肝癌和前列腺癌中上调。较高的 GSDMD 表达与原发性乳腺浸润性癌 (BRCA) 的生存率增加相关，但与肝细胞癌 (LIHC) 的生存率无关。在 BRCA 中（但在 LIHC 中则不然），高 GSDMD 表达与骨髓细胞特征相关，从而改善预后。为了进一步研究 GSDMD 在抗癌免疫中的作用，我们在 GSDMD 缺陷小鼠中诱导乳腺癌和肝癌肿瘤。与我们的预期相反，除了肝癌肿瘤中 Cxcl10 上调外，GSDMD 缺陷对肿瘤生长、免疫细胞浸润或肿瘤微环境中的细胞因子表达没有影响。 TLR 配体在体外和体内的先天免疫激活会引发炎症反应，结果显示 GSDMD 缺陷型小鼠和野生型小鼠之间没有显着差异。这些结果表明 GSDMD 对抗癌免疫的影响取决于肿瘤类型。他们强调了炎症通路在癌症中的复杂作用，强调需要进一步探索 GSDMD 在各种肿瘤微环境中的多方面影响。由于 GSDMD 的多种药理学调节剂可用，这可能会带来癌症联合治疗的新策略。版权所有 © 2024 Boersma、Puddinu、Huard、Fauteux-Daniel、Wirapati、Guedri、Tille、McKee、Pittet、Palmer 和 Bourquin。

Inflammation plays a pivotal role in cancer development, with chronic inflammation promoting tumor progression and treatment resistance, whereas acute inflammatory responses contribute to protective anti-tumor immunity. Gasdermin D (GSDMD) mediates the release of pro-inflammatory cytokines such as IL-1β. While the release of IL-1β is directly linked to the progression of several types of cancers, the role of GSDMD in cancer is less clear. In this study, we show that GSDMD expression is upregulated in human breast, kidney, liver, and prostate cancer. Higher GSDMD expression correlated with increased survival in primary breast invasive carcinoma (BRCA), but not in liver hepatocellular carcinoma (LIHC). In BRCA, but not in LIHC, high GSDMD expression correlated with a myeloid cell signature associated with improved prognosis. To further investigate the role of GSDMD in anticancer immunity, we induced breast cancer and hepatoma tumors in GSDMD-deficient mice. Contrary to our expectations, GSDMD deficiency had no effect on tumor growth, immune cell infiltration, or cytokine expression in the tumor microenvironment, except for Cxcl10 upregulation in hepatoma tumors. In vitro and in vivo innate immune activation with TLR ligands, that prime inflammatory responses, revealed no significant difference between GSDMD-deficient and wild-type mice. These results suggest that the impact of GSDMD on anticancer immunity is dependent on the tumor type. They underscore the complex role of inflammatory pathways in cancer, emphasizing the need for further exploration into the multifaceted effects of GSDMD in various tumor microenvironments. As several pharmacological modulators of GSDMD are available, this may lead to novel strategies for combination therapy in cancer.Copyright © 2024 Boersma, Puddinu, Huard, Fauteux-Daniel, Wirapati, Guedri, Tille, McKee, Pittet, Palmer and Bourquin.