CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer.
Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer.
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T H 2细胞和2型固有淋巴样细胞（ILC2）可通过分泌促肿瘤细胞因子如白细胞介素-4（IL-4）、IL-5和IL-13来刺激肿瘤生长。然而，2型免疫细胞向肿瘤微环境迁移的机制尚不清楚。在此，我们发现致癌性Kras G12D增加胰腺导管腺癌（PDAC）细胞中IL-33的表达，从而招募并激活T H 2和ILC2细胞。相应地，癌细胞特异性敲除IL-33可减少T H 2和ILC2的招募并促进肿瘤消退。出乎意料的是，IL-33的分泌依赖于瘤内真菌微生物组。基因敲除IL-33或抗真菌治疗可减少T H 2和ILC2浸润并提高生存率。一致地，在约20%的人类PDAC中观察到高IL-33表达，且表达主要局限于癌细胞。这些数据拓展了我们对驱动PDAC肿瘤进展机制的认识，并确定了涉及瘤内微生物组驱动的IL-33分泌的可治疗靶向通路。
T H 2 cells and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as interleukin-4 (IL-4), IL-5, and IL-13.
However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment are unknown.
Here, we show that oncogenic Kras G12D increases IL-33 expression in pancreatic ductal adenocarcinoma (PDAC) cells, which recruits and activates T H 2 and ILC2 cells. Correspondingly, cancer-cell-specific deletion of IL-33 reduces T H 2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, IL-33 secretion is dependent on the intratumoral fungal mycobiome.
Genetic deletion of IL-33 or anti-fungal treatment decreases T H 2 and ILC2 infiltration and increases survival. Consistently, high IL-33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identify therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL-33.
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