2. Academic Validation
  3. Tumour CD274 (PD-L1) expression and T cells in colorectal cancer

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

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.
PMID: 27196573 DOI: 10.1136/gutjnl-2016-311421
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.

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