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

Yohei Masugi, Reiko Nishihara, Juhong Yang, Kosuke Mima, Annacarolina Da Silva, Yan Shi, Kentaro Inamura, Yin Cao, Mingyang Song, Jonathan A. Nowak, Xiaoyun Liao, Katsuhiko Nosho, Andrew T. Chan, Marios Giannakis, Adam J. Bass, F. Stephen Hodi, Gordon J. Freeman, Scott Rodig, Charles S. Fuchs, Zhi Rong QianShuji Ogino

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71 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1463-1473
Number of pages11
JournalGut
Volume66
Issue number8
DOIs
Publication statusPublished - 2017 Aug 1

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

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    Masugi, Y., Nishihara, R., Yang, J., Mima, K., Da Silva, A., Shi, Y., Inamura, K., Cao, Y., Song, M., Nowak, J. A., Liao, X., Nosho, K., Chan, A. T., Giannakis, M., Bass, A. J., Hodi, F. S., Freeman, G. J., Rodig, S., Fuchs, C. S., ... Ogino, S. (2017). Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. Gut, 66(8), 1463-1473. https://doi.org/10.1136/gutjnl-2016-311421