生物
FOXP3型
提吉特
结直肠癌
亚型
癌症
免疫系统
癌症研究
肿瘤微环境
肿瘤科
免疫学
内科学
T细胞
医学
遗传学
程序设计语言
计算机科学
作者
Kaisa Cui,Surui Yao,Han Zhang,Mingyue Zhou,Bingxin Liu,Yulin Cao,Bojian Fei,Shenglin Huang,Zhaohui Huang
出处
期刊:Oncogene
[Springer Nature]
日期:2021-02-24
卷期号:40 (11): 2130-2145
被引量:17
标识
DOI:10.1038/s41388-021-01677-w
摘要
Colorectal cancer (CRC) is characterized by a heterogeneous tumor microenvironment (TME) that regulates cancer progression and therapeutic response. Overexpression of FOXP3 and CTLA4 is associated with immunosuppressive TME and poor prognosis in many cancer types. However, opposite results were reported in CRC. Thus, we performed comprehensive analyses to evaluate the exact prognostic value of FOXP3 and CTLA4 in CRC. Here, the expression levels of FOXP3 and CTLA4 were used to construct a subtyping system based on >1200 CRC patients from multiple independent public datasets. We revealed that, in CRC patients with relatively high expression of FOXP3, there exist two different subpopulations with opposite survival patterns according to CLTA4 expression. We further established a method for evaluating all cohorts and identified a novel FOXP3HighCTLA4High* CRC risk subpopulation that accounts for 5-10% of CRC patients. Moreover, different methods of functional enrichment and immune evaluation were used to analyze the TME characteristics of different FOXP3/CTLA4 subtypes. The FOXP3HighCTLA4High* CRC risk subpopulation was characterized by an immune overdrive TME phenotype, including high immune cell infiltration, low tumor purity, high immune checkpoint levels, and TGF-β activation. Finally, the constructed FOXP3/CTLA4 subtyping system was further validated by quantitative RT-PCR, immunochemistry staining, and multicolor immunofluorescence in an independent CRC cohort we collected. This high-risk subpopulation was also observed in kidney cancers and low-grade glioma patients by a Pan-cancer analysis. Together, our study revealed that the established FOXP3/CTLA4 molecular subtyping system could be used to select treatment and management strategies for CRC and other cancers.
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