RT Journal Article
SR Electronic
T1 Tumour CD274 (PD-L1) expression and T cells in colorectal cancer
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1463
OP 1473
DO 10.1136/gutjnl-2016-311421
VO 66
IS 8
A1 Masugi, Yohei
A1 Nishihara, Reiko
A1 Yang, Juhong
A1 Mima, Kosuke
A1 da Silva, Annacarolina
A1 Shi, Yan
A1 Inamura, Kentaro
A1 Cao, Yin
A1 Song, Mingyang
A1 Nowak, Jonathan A
A1 Liao, Xiaoyun
A1 Nosho, Katsuhiko
A1 Chan, Andrew T
A1 Giannakis, Marios
A1 Bass, Adam J
A1 Hodi, F Stephen
A1 Freeman, Gordon J
A1 Rodig, Scott
A1 Fuchs, Charles S
A1 Qian, Zhi Rong
A1 Ogino, Shuji
YR 2017
UL http://gut.bmj.com/content/66/8/1463.abstract
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.