PT  - JOURNAL ARTICLE
AU  - Masugi, Yohei
AU  - Nishihara, Reiko
AU  - Yang, Juhong
AU  - Mima, Kosuke
AU  - da Silva, Annacarolina
AU  - Shi, Yan
AU  - Inamura, Kentaro
AU  - Cao, Yin
AU  - Song, Mingyang
AU  - Nowak, Jonathan A
AU  - Liao, Xiaoyun
AU  - Nosho, Katsuhiko
AU  - Chan, Andrew T
AU  - Giannakis, Marios
AU  - Bass, Adam J
AU  - Hodi, F Stephen
AU  - Freeman, Gordon J
AU  - Rodig, Scott
AU  - Fuchs, Charles S
AU  - Qian, Zhi Rong
AU  - Ogino, Shuji
TI  - Tumour CD274 (PD-L1) expression and T cells in colorectal cancer
AID  - 10.1136/gutjnl-2016-311421
DP  - 2017 Aug 01
TA  - Gut
PG  - 1463--1473
VI  - 66
IP  - 8
4099  - http://gut.bmj.com/content/66/8/1463.short
4100  - http://gut.bmj.com/content/66/8/1463.full
SO  - Gut2017 Aug 01; 66
AB  - Objective 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.Design 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.Results 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.Conclusions 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.