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Tumor-infiltrating CD39+CD8+ T cells determine poor prognosis and immune evasion in clear cell renal cell carcinoma patients
Purpose Tumor microenvironment is important in the progression of clear cell renal cell carcinoma (ccRCC), and its prognostic value is still unclear. Recent reports demonstrated tumor-infiltrating CD39 + CD8 + T cells are abundant, but their function remains obscure. We aim to assess clinical value...
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| Published in: | Cancer Immunology, Immunotherapy Immunotherapy, 2020-08, Vol.69 (8), p.1565-1576 |
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| container_title | Cancer Immunology, Immunotherapy |
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| creator | Qi, Yu Xia, Yu Lin, Zhiyuan Qu, Yang Qi, Yangyang Chen, Yifan Zhou, Quan Zeng, Han Wang, Jiajun Chang, Yuan Bai, Qi Wang, Yiwei Zhu, Yu Xu, Le Chen, Lingli Kong, Yunyi Zhang, Weijuan Dai, Bo Liu, Li Guo, Jianming Xu, Jiejie |
| description | Purpose
Tumor microenvironment is important in the progression of clear cell renal cell carcinoma (ccRCC), and its prognostic value is still unclear. Recent reports demonstrated tumor-infiltrating CD39
+
CD8
+
T cells are abundant, but their function remains obscure. We aim to assess clinical value of CD39
+
CD8
+
T cells and seek a potential therapeutic target in ccRCC.
Experimental design
We immunohistochemically evaluated clinical value of CD39
+
CD8
+
T cells in a retrospective Zhongshan Hospital cohort of 243 ccRCC patients. Fresh tumor samples (
n
= 48), non-tumor tissues and peripheral blood for flow cytometry analyses were collected to analyze immune cell functions from Zhongshan Hospital. The survival benefit of tyrosine kinase inhibitors (TKIs) in this subpopulation was evaluated. Kaplan–Meier analysis and COX regression model were applied for survival analyses. Bioinformatics analysis performed in TCGA KIRC cohort and the scRNA-seq cohort.
Results
We found that accumulation of CD39
+
CD8
+
T cells indicated poor prognosis (
p |
| doi_str_mv | 10.1007/s00262-020-02563-2 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11027701</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2421630760</sourcerecordid><originalsourceid>FETCH-LOGICAL-c405t-8e1db57dcfc0ec432762bf8bd639ba776bf9c47c98ccdbba8daa62c2ac7464c43</originalsourceid><addsrcrecordid>eNp9kUtr3TAQhUVpaG5u-we6KIJuCsHpSLIle1XCTfqAQDa3ayHL8q2CLbmSHSj0x3cSp-ljkYWQ0HxzjkaHkNcMzhiAep8BuOQFcMBVSVHwZ2TDSoFXdcWekw2IEgoFUB6Tk5xv8MChaV6QY8EFSFDVhvzcL2NMhQ-9H-ZkZh8OdHchmtPdRX1K99S6Yci0c7NLow-OTjEmOqV4CDH7TE3oqB_HBSvu1mQfA_WB2sGZdN9KkwtmWI_WJOtDHA2d0MeFOb8kR70Zsnv1sG_J14-X-93n4ur605fd-VVhS6jmonasayvV2d6Cszifkrzt67aTommNUrLtG1sq29TWdm1r6s4YyS03VpWyxIYt-bDqTks7us6idzKDnpIfTfqho_H630rw3_Qh3mrGgCsFDBXePSik-H1xedajz3dTmeDikjUXDUcvJRtE3_6H3sQl4S8gVXImBSgJSPGVsinmnFz_-BoG-i5dvaarMV19ny56bMmbv-d4bPkdJwJiBTKWwsGlP95PyP4CPOyyHQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2421630760</pqid></control><display><type>article</type><title>Tumor-infiltrating CD39+CD8+ T cells determine poor prognosis and immune evasion in clear cell renal cell carcinoma patients</title><source>PubMed Central(OpenAccess)</source><source>Springer Nature</source><creator>Qi, Yu ; Xia, Yu ; Lin, Zhiyuan ; Qu, Yang ; Qi, Yangyang ; Chen, Yifan ; Zhou, Quan ; Zeng, Han ; Wang, Jiajun ; Chang, Yuan ; Bai, Qi ; Wang, Yiwei ; Zhu, Yu ; Xu, Le ; Chen, Lingli ; Kong, Yunyi ; Zhang, Weijuan ; Dai, Bo ; Liu, Li ; Guo, Jianming ; Xu, Jiejie</creator><creatorcontrib>Qi, Yu ; Xia, Yu ; Lin, Zhiyuan ; Qu, Yang ; Qi, Yangyang ; Chen, Yifan ; Zhou, Quan ; Zeng, Han ; Wang, Jiajun ; Chang, Yuan ; Bai, Qi ; Wang, Yiwei ; Zhu, Yu ; Xu, Le ; Chen, Lingli ; Kong, Yunyi ; Zhang, Weijuan ; Dai, Bo ; Liu, Li ; Guo, Jianming ; Xu, Jiejie</creatorcontrib><description>Purpose
Tumor microenvironment is important in the progression of clear cell renal cell carcinoma (ccRCC), and its prognostic value is still unclear. Recent reports demonstrated tumor-infiltrating CD39
+
CD8
+
T cells are abundant, but their function remains obscure. We aim to assess clinical value of CD39
+
CD8
+
T cells and seek a potential therapeutic target in ccRCC.
Experimental design
We immunohistochemically evaluated clinical value of CD39
+
CD8
+
T cells in a retrospective Zhongshan Hospital cohort of 243 ccRCC patients. Fresh tumor samples (
n
= 48), non-tumor tissues and peripheral blood for flow cytometry analyses were collected to analyze immune cell functions from Zhongshan Hospital. The survival benefit of tyrosine kinase inhibitors (TKIs) in this subpopulation was evaluated. Kaplan–Meier analysis and COX regression model were applied for survival analyses. Bioinformatics analysis performed in TCGA KIRC cohort and the scRNA-seq cohort.
Results
We found that accumulation of CD39
+
CD8
+
T cells indicated poor prognosis (
p
< 0.0001) and indicated therapeutic benefit of TKIs therapy (
p
= 0.015). CD39
+
CD8
+
T cells showed decreased TNF-α and IFN-γ with elevated PD-1 and TIM-3 expression. Further analysis of tumor-infiltrating immune cell landscape in the ccRCC revealed the positive correlation between CD39
+
CD8
+
T cells and Tregs (
p
= 0.037) and M2-polarized macrophages (
p
< 0.0001). Finally, inhibition of CD39 partially restores the anti-tumor function of CD8
+
T cells.
Conclusions
High CD39
+
CD8
+
T cells indicated poor prognosis in ccRCC, due to impaired anti-tumor function of CD39
+
CD8
+
T cells and indicated therapeutic benefit of TKIs therapy.
Graphic abstract</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-020-02563-2</identifier><identifier>PMID: 32306075</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Antitumor activity ; Apyrase - antagonists & inhibitors ; Apyrase - metabolism ; Bioinformatics ; Biomarkers, Tumor - analysis ; Cancer Research ; Carcinoma, Renal Cell - drug therapy ; Carcinoma, Renal Cell - immunology ; Carcinoma, Renal Cell - metabolism ; Carcinoma, Renal Cell - pathology ; CD8 antigen ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Clear cell-type renal cell carcinoma ; Female ; Flow cytometry ; Follow-Up Studies ; Humans ; Immune evasion ; Immune Evasion - drug effects ; Immune Evasion - immunology ; Immunology ; Kidney cancer ; Kidney Neoplasms - drug therapy ; Kidney Neoplasms - immunology ; Kidney Neoplasms - metabolism ; Kidney Neoplasms - pathology ; Lymphocytes ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - drug effects ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - metabolism ; Macrophages ; Male ; Medical prognosis ; Medicine ; Medicine & Public Health ; Middle Aged ; Oncology ; Original ; Original Article ; Patients ; PD-1 protein ; Peripheral blood ; Prognosis ; Protein-tyrosine kinase ; Retrospective Studies ; Survival Rate ; Therapeutic applications ; Tumor Microenvironment - drug effects ; Tumor Microenvironment - immunology ; Tumor necrosis factor-α ; Young Adult ; γ-Interferon</subject><ispartof>Cancer Immunology, Immunotherapy, 2020-08, Vol.69 (8), p.1565-1576</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-8e1db57dcfc0ec432762bf8bd639ba776bf9c47c98ccdbba8daa62c2ac7464c43</citedby><cites>FETCH-LOGICAL-c405t-8e1db57dcfc0ec432762bf8bd639ba776bf9c47c98ccdbba8daa62c2ac7464c43</cites><orcidid>0000-0001-7431-9063</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027701/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027701/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32306075$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qi, Yu</creatorcontrib><creatorcontrib>Xia, Yu</creatorcontrib><creatorcontrib>Lin, Zhiyuan</creatorcontrib><creatorcontrib>Qu, Yang</creatorcontrib><creatorcontrib>Qi, Yangyang</creatorcontrib><creatorcontrib>Chen, Yifan</creatorcontrib><creatorcontrib>Zhou, Quan</creatorcontrib><creatorcontrib>Zeng, Han</creatorcontrib><creatorcontrib>Wang, Jiajun</creatorcontrib><creatorcontrib>Chang, Yuan</creatorcontrib><creatorcontrib>Bai, Qi</creatorcontrib><creatorcontrib>Wang, Yiwei</creatorcontrib><creatorcontrib>Zhu, Yu</creatorcontrib><creatorcontrib>Xu, Le</creatorcontrib><creatorcontrib>Chen, Lingli</creatorcontrib><creatorcontrib>Kong, Yunyi</creatorcontrib><creatorcontrib>Zhang, Weijuan</creatorcontrib><creatorcontrib>Dai, Bo</creatorcontrib><creatorcontrib>Liu, Li</creatorcontrib><creatorcontrib>Guo, Jianming</creatorcontrib><creatorcontrib>Xu, Jiejie</creatorcontrib><title>Tumor-infiltrating CD39+CD8+ T cells determine poor prognosis and immune evasion in clear cell renal cell carcinoma patients</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Purpose
Tumor microenvironment is important in the progression of clear cell renal cell carcinoma (ccRCC), and its prognostic value is still unclear. Recent reports demonstrated tumor-infiltrating CD39
+
CD8
+
T cells are abundant, but their function remains obscure. We aim to assess clinical value of CD39
+
CD8
+
T cells and seek a potential therapeutic target in ccRCC.
Experimental design
We immunohistochemically evaluated clinical value of CD39
+
CD8
+
T cells in a retrospective Zhongshan Hospital cohort of 243 ccRCC patients. Fresh tumor samples (
n
= 48), non-tumor tissues and peripheral blood for flow cytometry analyses were collected to analyze immune cell functions from Zhongshan Hospital. The survival benefit of tyrosine kinase inhibitors (TKIs) in this subpopulation was evaluated. Kaplan–Meier analysis and COX regression model were applied for survival analyses. Bioinformatics analysis performed in TCGA KIRC cohort and the scRNA-seq cohort.
Results
We found that accumulation of CD39
+
CD8
+
T cells indicated poor prognosis (
p
< 0.0001) and indicated therapeutic benefit of TKIs therapy (
p
= 0.015). CD39
+
CD8
+
T cells showed decreased TNF-α and IFN-γ with elevated PD-1 and TIM-3 expression. Further analysis of tumor-infiltrating immune cell landscape in the ccRCC revealed the positive correlation between CD39
+
CD8
+
T cells and Tregs (
p
= 0.037) and M2-polarized macrophages (
p
< 0.0001). Finally, inhibition of CD39 partially restores the anti-tumor function of CD8
+
T cells.
Conclusions
High CD39
+
CD8
+
T cells indicated poor prognosis in ccRCC, due to impaired anti-tumor function of CD39
+
CD8
+
T cells and indicated therapeutic benefit of TKIs therapy.
Graphic abstract</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Antitumor activity</subject><subject>Apyrase - antagonists & inhibitors</subject><subject>Apyrase - metabolism</subject><subject>Bioinformatics</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Cancer Research</subject><subject>Carcinoma, Renal Cell - drug therapy</subject><subject>Carcinoma, Renal Cell - immunology</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Clear cell-type renal cell carcinoma</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Immune evasion</subject><subject>Immune Evasion - drug effects</subject><subject>Immune Evasion - immunology</subject><subject>Immunology</subject><subject>Kidney cancer</subject><subject>Kidney Neoplasms - drug therapy</subject><subject>Kidney Neoplasms - immunology</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Kidney Neoplasms - pathology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphocytes, Tumor-Infiltrating - drug effects</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - metabolism</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>Peripheral blood</subject><subject>Prognosis</subject><subject>Protein-tyrosine kinase</subject><subject>Retrospective Studies</subject><subject>Survival Rate</subject><subject>Therapeutic applications</subject><subject>Tumor Microenvironment - drug effects</subject><subject>Tumor Microenvironment - immunology</subject><subject>Tumor necrosis factor-α</subject><subject>Young Adult</subject><subject>γ-Interferon</subject><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kUtr3TAQhUVpaG5u-we6KIJuCsHpSLIle1XCTfqAQDa3ayHL8q2CLbmSHSj0x3cSp-ljkYWQ0HxzjkaHkNcMzhiAep8BuOQFcMBVSVHwZ2TDSoFXdcWekw2IEgoFUB6Tk5xv8MChaV6QY8EFSFDVhvzcL2NMhQ-9H-ZkZh8OdHchmtPdRX1K99S6Yci0c7NLow-OTjEmOqV4CDH7TE3oqB_HBSvu1mQfA_WB2sGZdN9KkwtmWI_WJOtDHA2d0MeFOb8kR70Zsnv1sG_J14-X-93n4ur605fd-VVhS6jmonasayvV2d6Cszifkrzt67aTommNUrLtG1sq29TWdm1r6s4YyS03VpWyxIYt-bDqTks7us6idzKDnpIfTfqho_H630rw3_Qh3mrGgCsFDBXePSik-H1xedajz3dTmeDikjUXDUcvJRtE3_6H3sQl4S8gVXImBSgJSPGVsinmnFz_-BoG-i5dvaarMV19ny56bMmbv-d4bPkdJwJiBTKWwsGlP95PyP4CPOyyHQ</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Qi, Yu</creator><creator>Xia, Yu</creator><creator>Lin, Zhiyuan</creator><creator>Qu, Yang</creator><creator>Qi, Yangyang</creator><creator>Chen, Yifan</creator><creator>Zhou, Quan</creator><creator>Zeng, Han</creator><creator>Wang, Jiajun</creator><creator>Chang, Yuan</creator><creator>Bai, Qi</creator><creator>Wang, Yiwei</creator><creator>Zhu, Yu</creator><creator>Xu, Le</creator><creator>Chen, Lingli</creator><creator>Kong, Yunyi</creator><creator>Zhang, Weijuan</creator><creator>Dai, Bo</creator><creator>Liu, Li</creator><creator>Guo, Jianming</creator><creator>Xu, Jiejie</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7431-9063</orcidid></search><sort><creationdate>20200801</creationdate><title>Tumor-infiltrating CD39+CD8+ T cells determine poor prognosis and immune evasion in clear cell renal cell carcinoma patients</title><author>Qi, Yu ; Xia, Yu ; Lin, Zhiyuan ; Qu, Yang ; Qi, Yangyang ; Chen, Yifan ; Zhou, Quan ; Zeng, Han ; Wang, Jiajun ; Chang, Yuan ; Bai, Qi ; Wang, Yiwei ; Zhu, Yu ; Xu, Le ; Chen, Lingli ; Kong, Yunyi ; Zhang, Weijuan ; Dai, Bo ; Liu, Li ; Guo, Jianming ; Xu, Jiejie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-8e1db57dcfc0ec432762bf8bd639ba776bf9c47c98ccdbba8daa62c2ac7464c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Antitumor activity</topic><topic>Apyrase - antagonists & inhibitors</topic><topic>Apyrase - metabolism</topic><topic>Bioinformatics</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Cancer Research</topic><topic>Carcinoma, Renal Cell - drug therapy</topic><topic>Carcinoma, Renal Cell - immunology</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>Carcinoma, Renal Cell - pathology</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - drug effects</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Clear cell-type renal cell carcinoma</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Immune evasion</topic><topic>Immune Evasion - drug effects</topic><topic>Immune Evasion - immunology</topic><topic>Immunology</topic><topic>Kidney cancer</topic><topic>Kidney Neoplasms - drug therapy</topic><topic>Kidney Neoplasms - immunology</topic><topic>Kidney Neoplasms - metabolism</topic><topic>Kidney Neoplasms - pathology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Lymphocytes, Tumor-Infiltrating - drug effects</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - metabolism</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Patients</topic><topic>PD-1 protein</topic><topic>Peripheral blood</topic><topic>Prognosis</topic><topic>Protein-tyrosine kinase</topic><topic>Retrospective Studies</topic><topic>Survival Rate</topic><topic>Therapeutic applications</topic><topic>Tumor Microenvironment - drug effects</topic><topic>Tumor Microenvironment - immunology</topic><topic>Tumor necrosis factor-α</topic><topic>Young Adult</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qi, Yu</creatorcontrib><creatorcontrib>Xia, Yu</creatorcontrib><creatorcontrib>Lin, Zhiyuan</creatorcontrib><creatorcontrib>Qu, Yang</creatorcontrib><creatorcontrib>Qi, Yangyang</creatorcontrib><creatorcontrib>Chen, Yifan</creatorcontrib><creatorcontrib>Zhou, Quan</creatorcontrib><creatorcontrib>Zeng, Han</creatorcontrib><creatorcontrib>Wang, Jiajun</creatorcontrib><creatorcontrib>Chang, Yuan</creatorcontrib><creatorcontrib>Bai, Qi</creatorcontrib><creatorcontrib>Wang, Yiwei</creatorcontrib><creatorcontrib>Zhu, Yu</creatorcontrib><creatorcontrib>Xu, Le</creatorcontrib><creatorcontrib>Chen, Lingli</creatorcontrib><creatorcontrib>Kong, Yunyi</creatorcontrib><creatorcontrib>Zhang, Weijuan</creatorcontrib><creatorcontrib>Dai, Bo</creatorcontrib><creatorcontrib>Liu, Li</creatorcontrib><creatorcontrib>Guo, Jianming</creatorcontrib><creatorcontrib>Xu, Jiejie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qi, Yu</au><au>Xia, Yu</au><au>Lin, Zhiyuan</au><au>Qu, Yang</au><au>Qi, Yangyang</au><au>Chen, Yifan</au><au>Zhou, Quan</au><au>Zeng, Han</au><au>Wang, Jiajun</au><au>Chang, Yuan</au><au>Bai, Qi</au><au>Wang, Yiwei</au><au>Zhu, Yu</au><au>Xu, Le</au><au>Chen, Lingli</au><au>Kong, Yunyi</au><au>Zhang, Weijuan</au><au>Dai, Bo</au><au>Liu, Li</au><au>Guo, Jianming</au><au>Xu, Jiejie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor-infiltrating CD39+CD8+ T cells determine poor prognosis and immune evasion in clear cell renal cell carcinoma patients</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>69</volume><issue>8</issue><spage>1565</spage><epage>1576</epage><pages>1565-1576</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Purpose
Tumor microenvironment is important in the progression of clear cell renal cell carcinoma (ccRCC), and its prognostic value is still unclear. Recent reports demonstrated tumor-infiltrating CD39
+
CD8
+
T cells are abundant, but their function remains obscure. We aim to assess clinical value of CD39
+
CD8
+
T cells and seek a potential therapeutic target in ccRCC.
Experimental design
We immunohistochemically evaluated clinical value of CD39
+
CD8
+
T cells in a retrospective Zhongshan Hospital cohort of 243 ccRCC patients. Fresh tumor samples (
n
= 48), non-tumor tissues and peripheral blood for flow cytometry analyses were collected to analyze immune cell functions from Zhongshan Hospital. The survival benefit of tyrosine kinase inhibitors (TKIs) in this subpopulation was evaluated. Kaplan–Meier analysis and COX regression model were applied for survival analyses. Bioinformatics analysis performed in TCGA KIRC cohort and the scRNA-seq cohort.
Results
We found that accumulation of CD39
+
CD8
+
T cells indicated poor prognosis (
p
< 0.0001) and indicated therapeutic benefit of TKIs therapy (
p
= 0.015). CD39
+
CD8
+
T cells showed decreased TNF-α and IFN-γ with elevated PD-1 and TIM-3 expression. Further analysis of tumor-infiltrating immune cell landscape in the ccRCC revealed the positive correlation between CD39
+
CD8
+
T cells and Tregs (
p
= 0.037) and M2-polarized macrophages (
p
< 0.0001). Finally, inhibition of CD39 partially restores the anti-tumor function of CD8
+
T cells.
Conclusions
High CD39
+
CD8
+
T cells indicated poor prognosis in ccRCC, due to impaired anti-tumor function of CD39
+
CD8
+
T cells and indicated therapeutic benefit of TKIs therapy.
Graphic abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32306075</pmid><doi>10.1007/s00262-020-02563-2</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-7431-9063</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-7004 |
| ispartof | Cancer Immunology, Immunotherapy, 2020-08, Vol.69 (8), p.1565-1576 |
| issn | 0340-7004 1432-0851 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11027701 |
| source | PubMed Central(OpenAccess); Springer Nature |
| subjects | Adolescent Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Antitumor activity Apyrase - antagonists & inhibitors Apyrase - metabolism Bioinformatics Biomarkers, Tumor - analysis Cancer Research Carcinoma, Renal Cell - drug therapy Carcinoma, Renal Cell - immunology Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - pathology CD8 antigen CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Clear cell-type renal cell carcinoma Female Flow cytometry Follow-Up Studies Humans Immune evasion Immune Evasion - drug effects Immune Evasion - immunology Immunology Kidney cancer Kidney Neoplasms - drug therapy Kidney Neoplasms - immunology Kidney Neoplasms - metabolism Kidney Neoplasms - pathology Lymphocytes Lymphocytes T Lymphocytes, Tumor-Infiltrating - drug effects Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism Macrophages Male Medical prognosis Medicine Medicine & Public Health Middle Aged Oncology Original Original Article Patients PD-1 protein Peripheral blood Prognosis Protein-tyrosine kinase Retrospective Studies Survival Rate Therapeutic applications Tumor Microenvironment - drug effects Tumor Microenvironment - immunology Tumor necrosis factor-α Young Adult γ-Interferon |
| title | Tumor-infiltrating CD39+CD8+ T cells determine poor prognosis and immune evasion in clear cell renal cell carcinoma patients |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T21%3A56%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tumor-infiltrating%20CD39+CD8+%20T%20cells%20determine%20poor%20prognosis%20and%20immune%20evasion%20in%20clear%20cell%20renal%20cell%20carcinoma%20patients&rft.jtitle=Cancer%20Immunology,%20Immunotherapy&rft.au=Qi,%20Yu&rft.date=2020-08-01&rft.volume=69&rft.issue=8&rft.spage=1565&rft.epage=1576&rft.pages=1565-1576&rft.issn=0340-7004&rft.eissn=1432-0851&rft_id=info:doi/10.1007/s00262-020-02563-2&rft_dat=%3Cproquest_pubme%3E2421630760%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c405t-8e1db57dcfc0ec432762bf8bd639ba776bf9c47c98ccdbba8daa62c2ac7464c43%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2421630760&rft_id=info:pmid/32306075&rfr_iscdi=true |