Advanced

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer : Relationship with sidedness and prognosis

Berntsson, Jonna LU ; Eberhard, Jakob LU ; Nodin, Björn LU ; Leandersson, Karin LU ; Larsson, Anna H. LU and Jirström, Karin LU (2018) In OncoImmunology
Abstract

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 has been demonstrated to confer a prognostic value in colorectal cancer (CRC), but no studies have investigated whether this association differs according to tumour location. In this study, immunohistochemical expression of PD-1 and PD-L1 was analysed in tissue microarrays with primary tumours from 557 incident CRC cases from a prospective population-based cohort. Univariable and multivariable Cox regression analyses, adjusted for age, sex, TNM stage, differentiation grade and vascular invasion, were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and... (More)

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 has been demonstrated to confer a prognostic value in colorectal cancer (CRC), but no studies have investigated whether this association differs according to tumour location. In this study, immunohistochemical expression of PD-1 and PD-L1 was analysed in tissue microarrays with primary tumours from 557 incident CRC cases from a prospective population-based cohort. Univariable and multivariable Cox regression analyses, adjusted for age, sex, TNM stage, differentiation grade and vascular invasion, were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. High PD-L1 expression on tumour-infiltrating immune cells was an independent factor of a prolonged OS in the entire cohort (hazard ratio [HR] = 0.49; 95% confidence interval [CI] CI 0.35 – 0.68), and in tumours of the right colon (HR = 0.43; 95% CI 0.25 – 0.74) and the left colon (HR = 0.28; 95% CI 0.13 – 0.61), but not in rectal cancer. Tumour-specific PD-L1-expression was not prognostic, neither in the full cohort nor according to tumour location. High immune cell-specific PD-1 expression was associated with a prolonged OS in the entire cohort and in tumours of the right colon, but not in the left colon or rectum, and only in univariable analysis. In conclusion, these results demonstrate that immune cell-specific PD-L1 and PD-1 expression is prognostic in a site-dependent manner, whereas tumour-specific PD-L1-expression is not prognostic in CRC.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
colorectal cancer, PD-1, PD-L1, prognosis, programmed cell death receptor, sidedness, tumour location
in
OncoImmunology
publisher
Landes Bioscience
external identifiers
  • scopus:85048363747
ISSN
2162-4011
DOI
10.1080/2162402X.2018.1465165
language
English
LU publication?
yes
id
704f9d73-8d76-46a8-93db-42cf3ea24c1b
date added to LUP
2018-06-26 14:14:25
date last changed
2019-03-19 03:56:42
@article{704f9d73-8d76-46a8-93db-42cf3ea24c1b,
  abstract     = {<p>Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 has been demonstrated to confer a prognostic value in colorectal cancer (CRC), but no studies have investigated whether this association differs according to tumour location. In this study, immunohistochemical expression of PD-1 and PD-L1 was analysed in tissue microarrays with primary tumours from 557 incident CRC cases from a prospective population-based cohort. Univariable and multivariable Cox regression analyses, adjusted for age, sex, TNM stage, differentiation grade and vascular invasion, were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. High PD-L1 expression on tumour-infiltrating immune cells was an independent factor of a prolonged OS in the entire cohort (hazard ratio [HR] = 0.49; 95% confidence interval [CI] CI 0.35 – 0.68), and in tumours of the right colon (HR = 0.43; 95% CI 0.25 – 0.74) and the left colon (HR = 0.28; 95% CI 0.13 – 0.61), but not in rectal cancer. Tumour-specific PD-L1-expression was not prognostic, neither in the full cohort nor according to tumour location. High immune cell-specific PD-1 expression was associated with a prolonged OS in the entire cohort and in tumours of the right colon, but not in the left colon or rectum, and only in univariable analysis. In conclusion, these results demonstrate that immune cell-specific PD-L1 and PD-1 expression is prognostic in a site-dependent manner, whereas tumour-specific PD-L1-expression is not prognostic in CRC.</p>},
  author       = {Berntsson, Jonna and Eberhard, Jakob and Nodin, Björn and Leandersson, Karin and Larsson, Anna H. and Jirström, Karin},
  issn         = {2162-4011},
  keyword      = {colorectal cancer,PD-1,PD-L1,prognosis,programmed cell death receptor,sidedness,tumour location},
  language     = {eng},
  month        = {06},
  publisher    = {Landes Bioscience},
  series       = {OncoImmunology},
  title        = {Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer : Relationship with sidedness and prognosis},
  url          = {http://dx.doi.org/10.1080/2162402X.2018.1465165},
  year         = {2018},
}