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Tumour CD274 (PD-L1) expression and T cells in colorectal cancer
  1. Yohei Masugi1,
  2. Reiko Nishihara1,2,3,4,
  3. Juhong Yang1,5,
  4. Kosuke Mima1,
  5. Annacarolina da Silva1,
  6. Yan Shi1,
  7. Kentaro Inamura6,
  8. Yin Cao2,7,8,
  9. Mingyang Song2,7,8,
  10. Jonathan A Nowak9,
  11. Xiaoyun Liao1,10,
  12. Katsuhiko Nosho11,
  13. Andrew T Chan7,8,12,
  14. Marios Giannakis1,13,14,
  15. Adam J Bass1,13,14,
  16. F Stephen Hodi1,10,
  17. Gordon J Freeman1,14,
  18. Scott Rodig15,
  19. Charles S Fuchs1,12,
  20. Zhi Rong Qian1,
  21. Shuji Ogino1,3,9
  1. 1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
  2. 2Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  3. 3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  4. 4Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  5. 5Collaborative 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. 6Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
  7. 7Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  8. 8Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
  9. 9Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  10. 10Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
  11. 11Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
  12. 12Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  13. 13Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
  14. 14Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  15. 15Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Shuji Ogino, Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, 450 Brookline Avenue, DFCI Room M422, Boston, MA 02215 USA; shuji_ogino{at}dfci.harvard.edu

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.

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

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