肿瘤微环境
免疫系统
FOXP3型
免疫疗法
结直肠癌
CD8型
癌症研究
癌症免疫疗法
T细胞
白细胞介素2受体
化学
癌症
医学
免疫学
内科学
作者
Taohua Yue,Jichang Li,Jing Zhu,Shuai Zuo,Xin Wang,Yucun Liu,Jia Liu,Xiaoyun Liu,Pengyuan Wang,Shanwen Chen
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2022-12-16
卷期号:83 (4): 595-612
被引量:9
标识
DOI:10.1158/0008-5472.can-22-1837
摘要
Abstract Immunotherapy can elicit robust anticancer responses in the clinic. However, a large proportion of patients with colorectal cancer do not benefit from treatment. Although previous studies have shown that hydrogen sulfide (H2S) is involved in colorectal cancer development and immune escape, further insights into the mechanisms and related molecules are needed to identify approaches to reverse the tumor-supportive functions of H2S. Here, we observed significantly increased H2S levels in colorectal cancer tissues. Decreasing H2S levels by using CBS+/− mice or feeding mice a sulfur amino acid-restricted diet (SARD) led to a marked decrease in differentiated CD4+CD25+Foxp3+ Tregs and an increase in the CD8+ T-cell/Treg ratio. Endogenous or exogenous H2S depletion enhanced the efficacy of anti–PD-L1 and anti–CTLA4 treatment. H2S promoted Treg activation through the persulfidation of ENO1 at cysteine 119. Furthermore, H2S inhibited the migration of CD8+ T cells by increasing the expression of AAK-1 via ELK4 persulfidation at cysteine 25. Overall, reducing H2S levels engenders a favorable immune microenvironment in colorectal cancer by decreasing the persulfidation of ENO1 in Tregs and ELK4 in CD8+ T cells. SARD represents a potential dietary approach to promote responses to immunotherapies in colorectal cancer. Significance: H2S depletion increases the CD8+ T-cell/Treg ratio and enhances the efficacy of anti–PD-L1 and anti–CTLA4 treatment in colon cancer, identifying H2S as an anticancer immunotherapy target.
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