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Gut. 2017 Aug;66(8):1463-1473. doi: 10.1136/gutjnl-2016-311421. Epub 2016 May 5.

Tumour CD274 (PD-L1) expression and T cells in colorectal cancer.

Masugi Y1, Nishihara R1,2,3,4, Yang J1,5, Mima K1, da Silva A1, Shi Y1, Inamura K6, Cao Y2,7,8, Song M2,7,8, Nowak JA9, Liao X1,10, Nosho K11, Chan AT7,8,12, Giannakis M1,13,14, Bass AJ1,13,14, Hodi FS1,10, Freeman GJ1,14, Rodig S15, Fuchs CS1,12, Qian ZR1, Ogino S1,3,9.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
2
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
3
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
4
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
5
Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development, Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
6
Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
7
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
8
Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.
9
Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
10
Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
11
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
12
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
13
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
14
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
15
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Abstract

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.

KEYWORDS:

CANCER EPIDEMIOLOGY; COLORECTAL CANCER; IMMUNE RESPONSE; MOLECULAR PATHOLOGY; T LYMPHOCYTES

PMID:
27196573
PMCID:
PMC5097696
DOI:
10.1136/gutjnl-2016-311421
[Indexed for MEDLINE]
Free PMC Article

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