肠道微生物群和不变的自然杀伤 T (iNKT) 细胞之间的相互作用在结直肠癌 (CRC) 中发挥着关键作用。致病菌具核梭杆菌影响 CRC 浸润 iNKT 细胞的抗肿瘤功能。然而，与结直肠癌相关的其他细菌（如牙龈卟啉单胞菌）对其激活状态的影响仍有待探索。在这项研究中，我们证明粘膜相关牙龈卟啉单胞菌在 iNKT 细胞中诱导促肿瘤表型，随后影响肿瘤微环境中单核吞噬细胞的组成。从机制上讲，体内和体外实验表明，牙龈卟啉单胞菌可降低 iNKT 细胞的细胞毒性功能，通过增加几丁质酶 3-like-1 蛋白 (CHI3L1) 的表达来阻碍 iNKT 细胞裂解机制。 CHI3L1 的中和可有效恢复 iNKT 细胞的细胞毒性功能，表明具有重新激活 iNKT 细胞介导的抗肿瘤免疫的治疗潜力。总之，我们的数据证明了牙龈卟啉单胞菌如何通过诱导 iNKT 细胞中 CHI3L1 的上调来加速 CRC 进展，从而损害其细胞毒功能并促进宿主肿瘤免疫逃避。

The interaction between the gut microbiota and invariant Natural Killer T (iNKT) cells plays a pivotal role in colorectal cancer (CRC). The pathobiont Fusobacterium nucleatum influences the anti-tumor functions of CRC-infiltrating iNKT cells. However, the impact of other bacteria associated with CRC, like Porphyromonas gingivalis, on their activation status remains unexplored. In this study, we demonstrate that mucosa-associated P. gingivalis induces a protumour phenotype in iNKT cells, subsequently influencing the composition of mononuclear-phagocyte cells within the tumor microenvironment. Mechanistically, in vivo and in vitro experiments showed that P. gingivalis reduces the cytotoxic functions of iNKT cells, hampering the iNKT cell lytic machinery through increased expression of chitinase 3-like-1 protein (CHI3L1). Neutralization of CHI3L1 effectively restores iNKT cell cytotoxic functions suggesting a therapeutic potential to reactivate iNKT cell-mediated antitumour immunity. In conclusion, our data demonstrate how P. gingivalis accelerates CRC progression by inducing the upregulation of CHI3L1 in iNKT cells, thus impairing their cytotoxic functions and promoting host tumor immune evasion.