微卫星不稳定性
结直肠癌
癌症研究
CD8型
FOXP3型
克拉斯
癌症
免疫检查点
生物
肿瘤科
医学
免疫系统
内科学
免疫学
免疫疗法
基因
等位基因
微卫星
生物化学
作者
Yohei Masugi,Reiko Nishihara,Juhong Yang,Kosuke Mima,Annacarolina da Silva,Yan Shi,Kentaro Inamura,Yin Cao,Mingyang Song,Jonathan A. Nowak,Xiaoyun Liao,Katsuhiko Nosho,Andrew T. Chan,Marios Giannakis,Adam J. Bass,F. Stephen Hodi,Gordon J. Freeman,Scott J. Rodig,Charles S. Fuchs,Zhi Rong Qian,Shuji Ogino
出处
期刊:Gut
[BMJ]
日期:2016-05-05
卷期号:66 (8): 1463-1473
被引量:160
标识
DOI:10.1136/gutjnl-2016-311421
摘要
Evidence suggests that CD274 (programmed death-ligand 1, B7-H1) immune checkpoint ligand repress antitumour immunity through its interaction with the PDCD1 (programmed cell death 1, PD-1) receptor of T lymphocytes in various tumours. We hypothesised that tumour CD274 expression levels might be inversely associated with T-cell densities in colorectal carcinoma tissue.We evaluated tumour CD274 expression by immunohistochemistry in 823 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study. We conducted multivariable ordinal logistic regression analyses to examine the association of tumour CD274 expression with CD3+, CD8+, CD45RO (PTPRC)+ or FOXP3+ cell density in tumour tissue, controlling for potential confounders including tumour status of microsatellite instability (MSI), CpG island methylator phenotype, long interspersed nucleotide element-1 methylation level and KRAS, BRAF and PIK3CA mutations.CD274 expression in tumour cells or stromal cells (including immune cells) was detected in 731 (89%) or 44 (5%) cases, respectively. Tumour CD274 expression level correlated inversely with FOXP3+ cell density in colorectal cancer tissue (outcome) (ptrend=0.0002). For a unit increase in outcome quartile categories, multivariable OR in the highest (vs lowest) CD274 expression score was 0.22 (95% CI 0.10 to 0.47). Tumour CD274 expression was inversely associated with MSI-high status (p=0.001). CD274 expression was not significantly associated with CD3+, CD8+ or CD45RO+ cell density, pathological lymphocytic reactions or patient survival prognosis.Tumour CD274 expression is inversely associated with FOXP3+ cell density in colorectal cancer tissue, suggesting a possible influence of CD274-expressing carcinoma cells on regulatory T cells in the tumour microenvironment.
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