Tumour CD274 (PD-L1) expression and T cells in colorectal cancer PMID: 27196573

ADC Targets in Oncology

2026-04-10

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

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

Yohei Masugi ¹ , Reiko Nishihara ¹ ² ³ ⁴ , Juhong Yang ¹ ⁵ , Kosuke Mima ¹ , Annacarolina da Silva ¹ , Yan Shi ¹ , Kentaro Inamura ⁶ , Yin Cao ² ⁷ ⁸ , Mingyang Song ² ⁷ ⁸ , Jonathan A Nowak ⁹ , Xiaoyun Liao ¹ ¹⁰ , Katsuhiko Nosho ¹¹ , Andrew T Chan ⁷ ⁸ ¹² , Marios Giannakis ¹ ¹³ ¹⁴ , Adam J Bass ¹ ¹³ ¹⁴ , F Stephen Hodi ¹ ¹⁰ , Gordon J Freeman ¹ ¹⁴ , Scott Rodig ¹⁵ , Charles S Fuchs ¹ ¹² , Zhi Rong Qian ¹ , Shuji Ogino ¹ ³ ⁹

Affiliations

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) (p_trend=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.