Expression of PD-L1 and SOX2 during rectal tumourigenesis: Potential mechanisms for immune escape and tumour cell invasion

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Abstract

Immunoediting is defined as a process whereby tumour cells develop the capacity to escape immune cell recognition. Accumulating evidence suggests that cancer stem-like cells (CSCs) have an enhanced capacity to interact with the immune system. The expression of CSCs and immune cell-associated markers has been demonstrated to change with disease progression from premalignant lesions to invasive cancer. The present study investigated the expression of putative CSC and immune cell-associated markers in different stages of progression from dysplasia to invasive malignancy in rectal lesions. Immunohistochemistry was performed for the CSC markers Lgr5 and SOX2 and the immune-associated markers CD8, Foxp3 and PD-L1 in 79 cases of endoscopically-excised rectal lesions, ranging from low grade adenoma (LG) to invasive adenocarcinoma (AdCa). CD8 and Foxp3 expression significantly increased with advances in disease progression [AdCa vs. LG: Odds ratio (OR) 4.33; 95% confidence interval (CI), 1.16-16.3; P=0.03 and OR, 40.5; 95% CI, 6.57-249.6; P<0.0001, respectively]. An increase in programmed death-ligand 1 (PD-L1) expression was also observed with disease progression (OR, 24.0; 95% CI, 4.23-136.2; P=0.0003). The expression of sex determining region Y-box 2 (SOX2) did not correlate with disease progression, although an elevated expression was observed in areas with high grade dysplasia. Increased PD-L1 expression may be a mechanism by which tumour cells evade immune recognition, facilitating tumour cell invasion in rectal cancer. The expression of SOX2 in areas with high grade dysplasia may indicate the de-differentiation of tumour cells, or the activation of migration pathways for invasion.

Original languageEnglish
Pages (from-to)5761-5768
Number of pages8
JournalOncology Letters
Volume16
Issue number5
DOIs
Publication statusPublished - 1 Nov 2018

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Tumor Escape
Neoplastic Stem Cells
Ligands
Disease Progression
Neoplasms
Odds Ratio
Confidence Intervals
Adenoma
Adenocarcinoma
Rectal Neoplasms
Cell Differentiation
Immune System
Biomarkers
Immunohistochemistry

Cite this

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title = "Expression of PD-L1 and SOX2 during rectal tumourigenesis: Potential mechanisms for immune escape and tumour cell invasion",
abstract = "Immunoediting is defined as a process whereby tumour cells develop the capacity to escape immune cell recognition. Accumulating evidence suggests that cancer stem-like cells (CSCs) have an enhanced capacity to interact with the immune system. The expression of CSCs and immune cell-associated markers has been demonstrated to change with disease progression from premalignant lesions to invasive cancer. The present study investigated the expression of putative CSC and immune cell-associated markers in different stages of progression from dysplasia to invasive malignancy in rectal lesions. Immunohistochemistry was performed for the CSC markers Lgr5 and SOX2 and the immune-associated markers CD8, Foxp3 and PD-L1 in 79 cases of endoscopically-excised rectal lesions, ranging from low grade adenoma (LG) to invasive adenocarcinoma (AdCa). CD8 and Foxp3 expression significantly increased with advances in disease progression [AdCa vs. LG: Odds ratio (OR) 4.33; 95{\%} confidence interval (CI), 1.16-16.3; P=0.03 and OR, 40.5; 95{\%} CI, 6.57-249.6; P<0.0001, respectively]. An increase in programmed death-ligand 1 (PD-L1) expression was also observed with disease progression (OR, 24.0; 95{\%} CI, 4.23-136.2; P=0.0003). The expression of sex determining region Y-box 2 (SOX2) did not correlate with disease progression, although an elevated expression was observed in areas with high grade dysplasia. Increased PD-L1 expression may be a mechanism by which tumour cells evade immune recognition, facilitating tumour cell invasion in rectal cancer. The expression of SOX2 in areas with high grade dysplasia may indicate the de-differentiation of tumour cells, or the activation of migration pathways for invasion.",
keywords = "Cancer stem cell, Colorectal cancer, Programmed death-ligand 1, Rectal, Sex determining region y-box 2, Tumourigenesis",
author = "Miller, {Tim J.} and McCoy, {Melanie J.} and Christine Hemmings and Barry Iacopetta and Platell, {Cameron F.}",
year = "2018",
month = "11",
day = "1",
doi = "10.3892/ol.2018.9337",
language = "English",
volume = "16",
pages = "5761--5768",
journal = "Oncology Letters",
issn = "1792-1074",
publisher = "Spandidos Publications",
number = "5",

}

TY - JOUR

T1 - Expression of PD-L1 and SOX2 during rectal tumourigenesis

T2 - Potential mechanisms for immune escape and tumour cell invasion

AU - Miller, Tim J.

AU - McCoy, Melanie J.

AU - Hemmings, Christine

AU - Iacopetta, Barry

AU - Platell, Cameron F.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Immunoediting is defined as a process whereby tumour cells develop the capacity to escape immune cell recognition. Accumulating evidence suggests that cancer stem-like cells (CSCs) have an enhanced capacity to interact with the immune system. The expression of CSCs and immune cell-associated markers has been demonstrated to change with disease progression from premalignant lesions to invasive cancer. The present study investigated the expression of putative CSC and immune cell-associated markers in different stages of progression from dysplasia to invasive malignancy in rectal lesions. Immunohistochemistry was performed for the CSC markers Lgr5 and SOX2 and the immune-associated markers CD8, Foxp3 and PD-L1 in 79 cases of endoscopically-excised rectal lesions, ranging from low grade adenoma (LG) to invasive adenocarcinoma (AdCa). CD8 and Foxp3 expression significantly increased with advances in disease progression [AdCa vs. LG: Odds ratio (OR) 4.33; 95% confidence interval (CI), 1.16-16.3; P=0.03 and OR, 40.5; 95% CI, 6.57-249.6; P<0.0001, respectively]. An increase in programmed death-ligand 1 (PD-L1) expression was also observed with disease progression (OR, 24.0; 95% CI, 4.23-136.2; P=0.0003). The expression of sex determining region Y-box 2 (SOX2) did not correlate with disease progression, although an elevated expression was observed in areas with high grade dysplasia. Increased PD-L1 expression may be a mechanism by which tumour cells evade immune recognition, facilitating tumour cell invasion in rectal cancer. The expression of SOX2 in areas with high grade dysplasia may indicate the de-differentiation of tumour cells, or the activation of migration pathways for invasion.

AB - Immunoediting is defined as a process whereby tumour cells develop the capacity to escape immune cell recognition. Accumulating evidence suggests that cancer stem-like cells (CSCs) have an enhanced capacity to interact with the immune system. The expression of CSCs and immune cell-associated markers has been demonstrated to change with disease progression from premalignant lesions to invasive cancer. The present study investigated the expression of putative CSC and immune cell-associated markers in different stages of progression from dysplasia to invasive malignancy in rectal lesions. Immunohistochemistry was performed for the CSC markers Lgr5 and SOX2 and the immune-associated markers CD8, Foxp3 and PD-L1 in 79 cases of endoscopically-excised rectal lesions, ranging from low grade adenoma (LG) to invasive adenocarcinoma (AdCa). CD8 and Foxp3 expression significantly increased with advances in disease progression [AdCa vs. LG: Odds ratio (OR) 4.33; 95% confidence interval (CI), 1.16-16.3; P=0.03 and OR, 40.5; 95% CI, 6.57-249.6; P<0.0001, respectively]. An increase in programmed death-ligand 1 (PD-L1) expression was also observed with disease progression (OR, 24.0; 95% CI, 4.23-136.2; P=0.0003). The expression of sex determining region Y-box 2 (SOX2) did not correlate with disease progression, although an elevated expression was observed in areas with high grade dysplasia. Increased PD-L1 expression may be a mechanism by which tumour cells evade immune recognition, facilitating tumour cell invasion in rectal cancer. The expression of SOX2 in areas with high grade dysplasia may indicate the de-differentiation of tumour cells, or the activation of migration pathways for invasion.

KW - Cancer stem cell

KW - Colorectal cancer

KW - Programmed death-ligand 1

KW - Rectal

KW - Sex determining region y-box 2

KW - Tumourigenesis

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U2 - 10.3892/ol.2018.9337

DO - 10.3892/ol.2018.9337

M3 - Article

VL - 16

SP - 5761

EP - 5768

JO - Oncology Letters

JF - Oncology Letters

SN - 1792-1074

IS - 5

ER -