Tumor-Associated CD[163.sup.+] M2 Macrophage Infiltration is Highly Associated with PD-L1 Expression in Cervical Cancer

Background: Programmed death-ligand 1 (PD-L1) is a negative costimulatory molecule, and its main function is widely considered to be in the regulation of T cells. Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment, and they also play an important role in immunosu...

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Published in:Cancer management and research 2020-07, Vol.12, p.5831
Main Authors: Guo, Fan, Feng, Yang-chun, Zhao, Gang, Zhang, Ran, Cheng, Zhen-zhen, Kong, Wei-na, Wu, Hui-li, Xu, Bin, Lv, Xiang, Ma, Xiu-min
Format: Article
Language:English
Subjects:
Analysis
B cells
Cervical cancer
Health aspects
Immunohistochemistry
Immunotherapy
Infiltration (Hydrology)
Macrophages
Pembrolizumab
Squamous cell carcinoma
T cells
Tumors
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container_title Cancer management and research
container_volume 12
creator Guo, Fan
Feng, Yang-chun
Zhao, Gang
Zhang, Ran
Cheng, Zhen-zhen
Kong, Wei-na
Wu, Hui-li
Xu, Bin
Lv, Xiang
Ma, Xiu-min
description Background: Programmed death-ligand 1 (PD-L1) is a negative costimulatory molecule, and its main function is widely considered to be in the regulation of T cells. Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment, and they also play an important role in immunosuppression. However, the relationship between the expression of PD-L1 and TAMs in cervical carcinoma (CC) remains unclear. We detected the expression of PD-L1 and TAMs in tumor tissue to study the correlation between them. Methods: Immunohistochemical staining of PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) was performed in 120 cases of cervical squamous cell carcinoma. Logistic regression analysis was used to evaluate the predictors related to positive PD-L1 expression. We also apply the Kaplan-Meier method to study the recurrence-free and overall survival rate of CC patients. Results: The increase in PD-L1 expression in tumor cells (TC) was significantly correlated with the increase in CD163 density (r=0.8550, p
doi_str_mv 10.2147/CMAR.S257692
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Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment, and they also play an important role in immunosuppression. However, the relationship between the expression of PD-L1 and TAMs in cervical carcinoma (CC) remains unclear. We detected the expression of PD-L1 and TAMs in tumor tissue to study the correlation between them. Methods: Immunohistochemical staining of PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) was performed in 120 cases of cervical squamous cell carcinoma. Logistic regression analysis was used to evaluate the predictors related to positive PD-L1 expression. We also apply the Kaplan-Meier method to study the recurrence-free and overall survival rate of CC patients. Results: The increase in PD-L1 expression in tumor cells (TC) was significantly correlated with the increase in CD163 density (r=0.8550, p&lt;0.0001), while PD-L1 in the stroma was also significantly associated with the intratumoral density of CD68- or CD163-positive cells (CD68 p&lt;0.0001; CD163 p=0.0009). The mean infiltration rates of CD68- and CD163-positive cells in PD-L1-positive TC were significantly higher than in PD-L1-negative TC (CD68 p=0.0095; CD163 p&lt;0.0001). In multivariate logistic regression analyses, only the density of CD163-positive cells was correlated with the expression of PD-L1 in TC cells (OR 1.52; p=0.032). In prognostic analysis, PD-L1 more than 10% was significantly correlated with short RFS (HR=2.66; p=0.028). For CD[163.sup.+] macrophage evaluation, the density above the median was also significantly correlated with RFS (HR=2.48; p=0.021). Conclusion: CD[163.sup.+] M2-like macrophage infiltration is highly associated with PD-L1 expression in CC, suggesting that macrophage infiltration can serve as a potential therapeutic target. Keywords: cervical cancer, programmed death-ligand 1, macrophages, tumor microenvironment</description><identifier>ISSN: 1179-1322</identifier><identifier>EISSN: 1179-1322</identifier><identifier>DOI: 10.2147/CMAR.S257692</identifier><language>eng</language><publisher>Dove Medical Press Limited</publisher><subject>Analysis ; B cells ; Cervical cancer ; Health aspects ; Immunohistochemistry ; Immunotherapy ; Infiltration (Hydrology) ; Macrophages ; Pembrolizumab ; Squamous cell carcinoma ; T cells ; Tumors</subject><ispartof>Cancer management and research, 2020-07, Vol.12, p.5831</ispartof><rights>COPYRIGHT 2020 Dove Medical Press Limited</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27900,27901</link.rule.ids></links><search><creatorcontrib>Guo, Fan</creatorcontrib><creatorcontrib>Feng, Yang-chun</creatorcontrib><creatorcontrib>Zhao, Gang</creatorcontrib><creatorcontrib>Zhang, Ran</creatorcontrib><creatorcontrib>Cheng, Zhen-zhen</creatorcontrib><creatorcontrib>Kong, Wei-na</creatorcontrib><creatorcontrib>Wu, Hui-li</creatorcontrib><creatorcontrib>Xu, Bin</creatorcontrib><creatorcontrib>Lv, Xiang</creatorcontrib><creatorcontrib>Ma, Xiu-min</creatorcontrib><title>Tumor-Associated CD[163.sup.+] M2 Macrophage Infiltration is Highly Associated with PD-L1 Expression in Cervical Cancer</title><title>Cancer management and research</title><description>Background: Programmed death-ligand 1 (PD-L1) is a negative costimulatory molecule, and its main function is widely considered to be in the regulation of T cells. Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment, and they also play an important role in immunosuppression. However, the relationship between the expression of PD-L1 and TAMs in cervical carcinoma (CC) remains unclear. We detected the expression of PD-L1 and TAMs in tumor tissue to study the correlation between them. Methods: Immunohistochemical staining of PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) was performed in 120 cases of cervical squamous cell carcinoma. Logistic regression analysis was used to evaluate the predictors related to positive PD-L1 expression. We also apply the Kaplan-Meier method to study the recurrence-free and overall survival rate of CC patients. Results: The increase in PD-L1 expression in tumor cells (TC) was significantly correlated with the increase in CD163 density (r=0.8550, p&lt;0.0001), while PD-L1 in the stroma was also significantly associated with the intratumoral density of CD68- or CD163-positive cells (CD68 p&lt;0.0001; CD163 p=0.0009). The mean infiltration rates of CD68- and CD163-positive cells in PD-L1-positive TC were significantly higher than in PD-L1-negative TC (CD68 p=0.0095; CD163 p&lt;0.0001). In multivariate logistic regression analyses, only the density of CD163-positive cells was correlated with the expression of PD-L1 in TC cells (OR 1.52; p=0.032). In prognostic analysis, PD-L1 more than 10% was significantly correlated with short RFS (HR=2.66; p=0.028). For CD[163.sup.+] macrophage evaluation, the density above the median was also significantly correlated with RFS (HR=2.48; p=0.021). Conclusion: CD[163.sup.+] M2-like macrophage infiltration is highly associated with PD-L1 expression in CC, suggesting that macrophage infiltration can serve as a potential therapeutic target. Keywords: cervical cancer, programmed death-ligand 1, macrophages, tumor microenvironment</description><subject>Analysis</subject><subject>B cells</subject><subject>Cervical cancer</subject><subject>Health aspects</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>Infiltration (Hydrology)</subject><subject>Macrophages</subject><subject>Pembrolizumab</subject><subject>Squamous cell carcinoma</subject><subject>T cells</subject><subject>Tumors</subject><issn>1179-1322</issn><issn>1179-1322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNptj19LwzAUxYMoOKdvfoCAj9Kam6RJ-1i6zQ02FN2byEjTpIt07Wg6p9_e-uehD3K43PPwO5d7ELoGElLg8i5bpU_hM42kSOgJGgHIJABG6enAn6ML798IEQkwPkLH9WHXtEHqfaOd6kyBs8kLCBb6wz68fcUrildKt81-q0qDF7V1VdeqzjU1dh7PXbmtPvEgfXTdFj9OgiXg6ce-Nd7_oDXOTPvutKpwpmpt2kt0ZlXlzdXfHqP1bLrO5sHy4X6RpcugFJIFlnGpBCOxBRrlABqE5TwyhWR5rhPQjBrJo-R7tC64FJEFQmICOcQkz9kY3fyeLVVlNq62Tf-93jmvN6lgNBaJjFlPhf9QvQqzc7qpTd_aDANfz8xq-A</recordid><startdate>20200731</startdate><enddate>20200731</enddate><creator>Guo, Fan</creator><creator>Feng, Yang-chun</creator><creator>Zhao, Gang</creator><creator>Zhang, Ran</creator><creator>Cheng, Zhen-zhen</creator><creator>Kong, Wei-na</creator><creator>Wu, Hui-li</creator><creator>Xu, Bin</creator><creator>Lv, Xiang</creator><creator>Ma, Xiu-min</creator><general>Dove Medical Press Limited</general><scope/></search><sort><creationdate>20200731</creationdate><title>Tumor-Associated CD[163.sup.+] M2 Macrophage Infiltration is Highly Associated with PD-L1 Expression in Cervical Cancer</title><author>Guo, Fan ; Feng, Yang-chun ; Zhao, Gang ; Zhang, Ran ; Cheng, Zhen-zhen ; Kong, Wei-na ; Wu, Hui-li ; Xu, Bin ; Lv, Xiang ; Ma, Xiu-min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g673-f347a6308f125b11c16f445ed73bbc91c32e74597459ccd4765f100801b180bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>B cells</topic><topic>Cervical cancer</topic><topic>Health aspects</topic><topic>Immunohistochemistry</topic><topic>Immunotherapy</topic><topic>Infiltration (Hydrology)</topic><topic>Macrophages</topic><topic>Pembrolizumab</topic><topic>Squamous cell carcinoma</topic><topic>T cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Fan</creatorcontrib><creatorcontrib>Feng, Yang-chun</creatorcontrib><creatorcontrib>Zhao, Gang</creatorcontrib><creatorcontrib>Zhang, Ran</creatorcontrib><creatorcontrib>Cheng, Zhen-zhen</creatorcontrib><creatorcontrib>Kong, Wei-na</creatorcontrib><creatorcontrib>Wu, Hui-li</creatorcontrib><creatorcontrib>Xu, Bin</creatorcontrib><creatorcontrib>Lv, Xiang</creatorcontrib><creatorcontrib>Ma, Xiu-min</creatorcontrib><jtitle>Cancer management and research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Fan</au><au>Feng, Yang-chun</au><au>Zhao, Gang</au><au>Zhang, Ran</au><au>Cheng, Zhen-zhen</au><au>Kong, Wei-na</au><au>Wu, Hui-li</au><au>Xu, Bin</au><au>Lv, Xiang</au><au>Ma, Xiu-min</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor-Associated CD[163.sup.+] M2 Macrophage Infiltration is Highly Associated with PD-L1 Expression in Cervical Cancer</atitle><jtitle>Cancer management and research</jtitle><date>2020-07-31</date><risdate>2020</risdate><volume>12</volume><spage>5831</spage><pages>5831-</pages><issn>1179-1322</issn><eissn>1179-1322</eissn><abstract>Background: Programmed death-ligand 1 (PD-L1) is a negative costimulatory molecule, and its main function is widely considered to be in the regulation of T cells. Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment, and they also play an important role in immunosuppression. However, the relationship between the expression of PD-L1 and TAMs in cervical carcinoma (CC) remains unclear. We detected the expression of PD-L1 and TAMs in tumor tissue to study the correlation between them. Methods: Immunohistochemical staining of PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) was performed in 120 cases of cervical squamous cell carcinoma. Logistic regression analysis was used to evaluate the predictors related to positive PD-L1 expression. We also apply the Kaplan-Meier method to study the recurrence-free and overall survival rate of CC patients. Results: The increase in PD-L1 expression in tumor cells (TC) was significantly correlated with the increase in CD163 density (r=0.8550, p&lt;0.0001), while PD-L1 in the stroma was also significantly associated with the intratumoral density of CD68- or CD163-positive cells (CD68 p&lt;0.0001; CD163 p=0.0009). The mean infiltration rates of CD68- and CD163-positive cells in PD-L1-positive TC were significantly higher than in PD-L1-negative TC (CD68 p=0.0095; CD163 p&lt;0.0001). In multivariate logistic regression analyses, only the density of CD163-positive cells was correlated with the expression of PD-L1 in TC cells (OR 1.52; p=0.032). In prognostic analysis, PD-L1 more than 10% was significantly correlated with short RFS (HR=2.66; p=0.028). For CD[163.sup.+] macrophage evaluation, the density above the median was also significantly correlated with RFS (HR=2.48; p=0.021). Conclusion: CD[163.sup.+] M2-like macrophage infiltration is highly associated with PD-L1 expression in CC, suggesting that macrophage infiltration can serve as a potential therapeutic target. Keywords: cervical cancer, programmed death-ligand 1, macrophages, tumor microenvironment</abstract><pub>Dove Medical Press Limited</pub><doi>10.2147/CMAR.S257692</doi></addata></record>
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subjects Analysis
B cells
Cervical cancer
Health aspects
Immunohistochemistry
Immunotherapy
Infiltration (Hydrology)
Macrophages
Pembrolizumab
Squamous cell carcinoma
T cells
Tumors
title Tumor-Associated CD[163.sup.+] M2 Macrophage Infiltration is Highly Associated with PD-L1 Expression in Cervical Cancer
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