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

Research output: Contribution to journalArticle

61 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
Externally publishedYes

Fingerprint

Colorectal Neoplasms
T-Lymphocytes
Neoplasms
Cell Count
Microsatellite Instability
Programmed Cell Death 1 Receptor
CD80 Antigens
Long Interspersed Nucleotide Elements
CpG Islands
Tumor Microenvironment
Health
Regulatory T-Lymphocytes
Rectal Neoplasms
Stromal Cells
Colonic Neoplasms
Methylation
Immunity
Cell Death
Logistic Models
Immunohistochemistry

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Masugi, Y., Nishihara, R., Yang, J., Mima, K., Da Silva, A., Shi, Y., ... 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

Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. / Masugi, Yohei; Nishihara, Reiko; Yang, Juhong; Mima, Kosuke; Da Silva, Annacarolina; Shi, Yan; Inamura, Kentaro; Cao, Yin; Song, Mingyang; Nowak, Jonathan A.; Liao, Xiaoyun; Nosho, Katsuhiko; Chan, Andrew T.; Giannakis, Marios; Bass, Adam J.; Hodi, F. Stephen; Freeman, Gordon J.; Rodig, Scott; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji.

In: Gut, Vol. 66, No. 8, 01.08.2017, p. 1463-1473.

Research output: Contribution to journalArticle

Masugi, Y, Nishihara, R, Yang, J, Mima, K, Da Silva, A, Shi, Y, Inamura, K, Cao, Y, Song, M, Nowak, JA, Liao, X, Nosho, K, Chan, AT, Giannakis, M, Bass, AJ, Hodi, FS, Freeman, GJ, Rodig, S, Fuchs, CS, Qian, ZR & Ogino, S 2017, 'Tumour CD274 (PD-L1) expression and T cells in colorectal cancer', Gut, vol. 66, no. 8, pp. 1463-1473. https://doi.org/10.1136/gutjnl-2016-311421
Masugi Y, Nishihara R, Yang J, Mima K, Da Silva A, Shi Y et al. Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. Gut. 2017 Aug 1;66(8):1463-1473. https://doi.org/10.1136/gutjnl-2016-311421
Masugi, Yohei ; Nishihara, Reiko ; Yang, Juhong ; Mima, Kosuke ; Da Silva, Annacarolina ; Shi, Yan ; Inamura, Kentaro ; Cao, Yin ; Song, Mingyang ; Nowak, Jonathan A. ; Liao, Xiaoyun ; Nosho, Katsuhiko ; Chan, Andrew T. ; Giannakis, Marios ; Bass, Adam J. ; Hodi, F. Stephen ; Freeman, Gordon J. ; Rodig, Scott ; Fuchs, Charles S. ; Qian, Zhi Rong ; Ogino, Shuji. / Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. In: Gut. 2017 ; Vol. 66, No. 8. pp. 1463-1473.
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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.",
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AU - Masugi, Yohei

AU - Nishihara, Reiko

AU - Yang, Juhong

AU - Mima, Kosuke

AU - Da Silva, Annacarolina

AU - Shi, Yan

AU - Inamura, Kentaro

AU - Cao, Yin

AU - Song, Mingyang

AU - Nowak, Jonathan A.

AU - Liao, Xiaoyun

AU - Nosho, Katsuhiko

AU - Chan, Andrew T.

AU - Giannakis, Marios

AU - Bass, Adam J.

AU - Hodi, F. Stephen

AU - Freeman, Gordon J.

AU - Rodig, Scott

AU - Fuchs, Charles S.

AU - Qian, Zhi Rong

AU - Ogino, Shuji

PY - 2017/8/1

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N2 - 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.

AB - 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.

KW - CANCER EPIDEMIOLOGY

KW - COLORECTAL CANCER

KW - IMMUNE RESPONSE

KW - MOLECULAR PATHOLOGY

KW - T LYMPHOCYTES

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