Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients
Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer. In this study, we have characterized the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2-restricted peptide, pCEA691-699, isolated from the peripheral T...
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| Veröffentlicht in: | Clinical cancer research 2017-10, Vol.23 (20), p.6178-6189 |
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| creator | Chen, Yuan Xue, Shao-An Behboudi, Shahriar Mohammad, Goran H Pereira, Stephen P Morris, Emma C |
| description | Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer. In this study, we have characterized the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2-restricted peptide, pCEA691-699, isolated from the peripheral T-cell repertoire of pancreatic cancer patients and sought to determine if
PD-L1 and TIM-3 blockade could enhance CTL function.
CD8
T-cell lines were generated from peripheral blood mononuclear cells of 18 HLA-A2
patients with pancreatic cancer and from 15 healthy controls.
peptide-specific responses were evaluated by flow cytometry after staining for intracellular cytokine production and carboxy fluorescein succinimydyl ester cytotoxicity assays using pancreatic cancer cell lines as targets.
Cytokine-secreting functional CEA691-specific CTL lines were successfully generated from 10 of 18 pancreatic cancer patients, with two CTL lines able to recognize and kill both CEA691 peptide-loaded T2 cells and CEA
HLA-A2
pancreatic cancer cell lines. In the presence of
PD-L1 blockade, functional CEA691-specific CD8
T-cell responses, including IFNγ secretion and proliferation, were enhanced, and this effect was more pronounced on Ag-specific T cells isolated from tumor draining lymph nodes.
These data demonstrate that CEA691-specific CTL can be readily expanded from the self-restricted T-cell repertoire of pancreatic cancer patients and that their function can be enhanced by PD-L1 blockade.
. |
| doi_str_mv | 10.1158/1078-0432.CCR-17-1185 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5683391</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1983416526</sourcerecordid><originalsourceid>FETCH-LOGICAL-c439t-9baf5be68e0d05748e4b256a4741c0dba83009c1a7cee1e83d56404a622a85113</originalsourceid><addsrcrecordid>eNpVkd1u1DAQRi0EoqXwCCBLXLv1xHbi3CCVdEsrrURVCreW40xalzRe7GTp8vQ46o_gxh5pvjkz0iHkPfBDAKWPgFeacSmKw6a5ZFAxAK1ekH1QqmKiKNXLXD9l9siblG45BwlcviZ7ha6ACxD75M_qnv7w20AvTtgajvIL9MJON7_tjn4egvtpO6SXuMWYMNGTXern0U0-jDT0tPHRzYOd_HhNm9Ux-7ZB53vv6BVtcBgS9WOGjS5izjja5BLjgvc4TuktedXbIeG7x_-AfD9dXTVnbP31y3lzvGZOinpidWt71WKpkXdcVVKjbAtVWllJcLxrrRac1w5s5RABtehUKbm0ZVFYrQDEAfn0wN3M7R12Lu-OdjCb6O9s3Jlgvfm_M_obcx22RpVaiHoBfHwExPBrxjSZ2zDHMd9soNZCQqmKMqfUQ8rFkFLE_nkDcLMoM4sOs-gwWZmByizK8tyHf897nnpyJP4CvyORrQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1983416526</pqid></control><display><type>article</type><title>Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Chen, Yuan ; Xue, Shao-An ; Behboudi, Shahriar ; Mohammad, Goran H ; Pereira, Stephen P ; Morris, Emma C</creator><creatorcontrib>Chen, Yuan ; Xue, Shao-An ; Behboudi, Shahriar ; Mohammad, Goran H ; Pereira, Stephen P ; Morris, Emma C</creatorcontrib><description>Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer. In this study, we have characterized the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2-restricted peptide, pCEA691-699, isolated from the peripheral T-cell repertoire of pancreatic cancer patients and sought to determine if
PD-L1 and TIM-3 blockade could enhance CTL function.
CD8
T-cell lines were generated from peripheral blood mononuclear cells of 18 HLA-A2
patients with pancreatic cancer and from 15 healthy controls.
peptide-specific responses were evaluated by flow cytometry after staining for intracellular cytokine production and carboxy fluorescein succinimydyl ester cytotoxicity assays using pancreatic cancer cell lines as targets.
Cytokine-secreting functional CEA691-specific CTL lines were successfully generated from 10 of 18 pancreatic cancer patients, with two CTL lines able to recognize and kill both CEA691 peptide-loaded T2 cells and CEA
HLA-A2
pancreatic cancer cell lines. In the presence of
PD-L1 blockade, functional CEA691-specific CD8
T-cell responses, including IFNγ secretion and proliferation, were enhanced, and this effect was more pronounced on Ag-specific T cells isolated from tumor draining lymph nodes.
These data demonstrate that CEA691-specific CTL can be readily expanded from the self-restricted T-cell repertoire of pancreatic cancer patients and that their function can be enhanced by PD-L1 blockade.
.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-17-1185</identifier><identifier>PMID: 28710313</identifier><language>eng</language><publisher>United States: American Association for Cancer Research Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antigens ; Antineoplastic Agents, Immunological - pharmacology ; B7-H1 Antigen - metabolism ; Biomarkers, Tumor ; Biotechnology ; Cancer ; Carcinoembryonic antigen ; Carcinoembryonic Antigen - immunology ; CD8 antigen ; Cell Line, Tumor ; Cytokines ; Cytokines - metabolism ; Cytometry ; Cytotoxicity ; Cytotoxicity, Immunologic - drug effects ; Cytotoxicity, Immunologic - immunology ; Experimental design ; Female ; Flow cytometry ; Fluorescein ; Hepatitis A Virus Cellular Receptor 2 - antagonists & inhibitors ; Hepatitis A Virus Cellular Receptor 2 - metabolism ; Histocompatibility antigen HLA ; Humans ; Immunophenotyping ; Immunotherapy ; Leukocytes (mononuclear) ; Lymph nodes ; Lymphocytes ; Lymphocytes T ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic cancer ; Pancreatic Neoplasms - immunology ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - mortality ; Pancreatic Neoplasms - pathology ; Patients ; PD-1 protein ; PD-L1 protein ; Peptides ; Peripheral blood mononuclear cells ; Programmed Cell Death 1 Receptor - metabolism ; Signal Transduction ; T cell receptors ; T-Cell Antigen Receptor Specificity - immunology ; T-Lymphocyte Subsets - drug effects ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism ; T-Lymphocytes, Cytotoxic - drug effects ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - metabolism ; Toxicity ; Tumor cell lines ; γ-Interferon</subject><ispartof>Clinical cancer research, 2017-10, Vol.23 (20), p.6178-6189</ispartof><rights>2017 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research Inc Oct 15, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-9baf5be68e0d05748e4b256a4741c0dba83009c1a7cee1e83d56404a622a85113</citedby><cites>FETCH-LOGICAL-c439t-9baf5be68e0d05748e4b256a4741c0dba83009c1a7cee1e83d56404a622a85113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3356,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28710313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Yuan</creatorcontrib><creatorcontrib>Xue, Shao-An</creatorcontrib><creatorcontrib>Behboudi, Shahriar</creatorcontrib><creatorcontrib>Mohammad, Goran H</creatorcontrib><creatorcontrib>Pereira, Stephen P</creatorcontrib><creatorcontrib>Morris, Emma C</creatorcontrib><title>Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer. In this study, we have characterized the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2-restricted peptide, pCEA691-699, isolated from the peripheral T-cell repertoire of pancreatic cancer patients and sought to determine if
PD-L1 and TIM-3 blockade could enhance CTL function.
CD8
T-cell lines were generated from peripheral blood mononuclear cells of 18 HLA-A2
patients with pancreatic cancer and from 15 healthy controls.
peptide-specific responses were evaluated by flow cytometry after staining for intracellular cytokine production and carboxy fluorescein succinimydyl ester cytotoxicity assays using pancreatic cancer cell lines as targets.
Cytokine-secreting functional CEA691-specific CTL lines were successfully generated from 10 of 18 pancreatic cancer patients, with two CTL lines able to recognize and kill both CEA691 peptide-loaded T2 cells and CEA
HLA-A2
pancreatic cancer cell lines. In the presence of
PD-L1 blockade, functional CEA691-specific CD8
T-cell responses, including IFNγ secretion and proliferation, were enhanced, and this effect was more pronounced on Ag-specific T cells isolated from tumor draining lymph nodes.
These data demonstrate that CEA691-specific CTL can be readily expanded from the self-restricted T-cell repertoire of pancreatic cancer patients and that their function can be enhanced by PD-L1 blockade.
.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens</subject><subject>Antineoplastic Agents, Immunological - pharmacology</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Biomarkers, Tumor</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Carcinoembryonic antigen</subject><subject>Carcinoembryonic Antigen - immunology</subject><subject>CD8 antigen</subject><subject>Cell Line, Tumor</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Cytometry</subject><subject>Cytotoxicity</subject><subject>Cytotoxicity, Immunologic - drug effects</subject><subject>Cytotoxicity, Immunologic - immunology</subject><subject>Experimental design</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Fluorescein</subject><subject>Hepatitis A Virus Cellular Receptor 2 - antagonists & inhibitors</subject><subject>Hepatitis A Virus Cellular Receptor 2 - metabolism</subject><subject>Histocompatibility antigen HLA</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Immunotherapy</subject><subject>Leukocytes (mononuclear)</subject><subject>Lymph nodes</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - immunology</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Peptides</subject><subject>Peripheral blood mononuclear cells</subject><subject>Programmed Cell Death 1 Receptor - metabolism</subject><subject>Signal Transduction</subject><subject>T cell receptors</subject><subject>T-Cell Antigen Receptor Specificity - immunology</subject><subject>T-Lymphocyte Subsets - drug effects</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><subject>T-Lymphocytes, Cytotoxic - drug effects</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - metabolism</subject><subject>Toxicity</subject><subject>Tumor cell lines</subject><subject>γ-Interferon</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkd1u1DAQRi0EoqXwCCBLXLv1xHbi3CCVdEsrrURVCreW40xalzRe7GTp8vQ46o_gxh5pvjkz0iHkPfBDAKWPgFeacSmKw6a5ZFAxAK1ekH1QqmKiKNXLXD9l9siblG45BwlcviZ7ha6ACxD75M_qnv7w20AvTtgajvIL9MJON7_tjn4egvtpO6SXuMWYMNGTXern0U0-jDT0tPHRzYOd_HhNm9Ux-7ZB53vv6BVtcBgS9WOGjS5izjja5BLjgvc4TuktedXbIeG7x_-AfD9dXTVnbP31y3lzvGZOinpidWt71WKpkXdcVVKjbAtVWllJcLxrrRac1w5s5RABtehUKbm0ZVFYrQDEAfn0wN3M7R12Lu-OdjCb6O9s3Jlgvfm_M_obcx22RpVaiHoBfHwExPBrxjSZ2zDHMd9soNZCQqmKMqfUQ8rFkFLE_nkDcLMoM4sOs-gwWZmByizK8tyHf897nnpyJP4CvyORrQ</recordid><startdate>20171015</startdate><enddate>20171015</enddate><creator>Chen, Yuan</creator><creator>Xue, Shao-An</creator><creator>Behboudi, Shahriar</creator><creator>Mohammad, Goran H</creator><creator>Pereira, Stephen P</creator><creator>Morris, Emma C</creator><general>American Association for Cancer Research Inc</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>7QO</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20171015</creationdate><title>Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients</title><author>Chen, Yuan ; Xue, Shao-An ; Behboudi, Shahriar ; Mohammad, Goran H ; Pereira, Stephen P ; Morris, Emma C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-9baf5be68e0d05748e4b256a4741c0dba83009c1a7cee1e83d56404a622a85113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antigens</topic><topic>Antineoplastic Agents, Immunological - pharmacology</topic><topic>B7-H1 Antigen - metabolism</topic><topic>Biomarkers, Tumor</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Carcinoembryonic antigen</topic><topic>Carcinoembryonic Antigen - immunology</topic><topic>CD8 antigen</topic><topic>Cell Line, Tumor</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Cytometry</topic><topic>Cytotoxicity</topic><topic>Cytotoxicity, Immunologic - drug effects</topic><topic>Cytotoxicity, Immunologic - immunology</topic><topic>Experimental design</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Fluorescein</topic><topic>Hepatitis A Virus Cellular Receptor 2 - antagonists & inhibitors</topic><topic>Hepatitis A Virus Cellular Receptor 2 - metabolism</topic><topic>Histocompatibility antigen HLA</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Immunotherapy</topic><topic>Leukocytes (mononuclear)</topic><topic>Lymph nodes</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - immunology</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - mortality</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Patients</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Peptides</topic><topic>Peripheral blood mononuclear cells</topic><topic>Programmed Cell Death 1 Receptor - metabolism</topic><topic>Signal Transduction</topic><topic>T cell receptors</topic><topic>T-Cell Antigen Receptor Specificity - immunology</topic><topic>T-Lymphocyte Subsets - drug effects</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - metabolism</topic><topic>T-Lymphocytes, Cytotoxic - drug effects</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Cytotoxic - metabolism</topic><topic>Toxicity</topic><topic>Tumor cell lines</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Yuan</creatorcontrib><creatorcontrib>Xue, Shao-An</creatorcontrib><creatorcontrib>Behboudi, Shahriar</creatorcontrib><creatorcontrib>Mohammad, Goran H</creatorcontrib><creatorcontrib>Pereira, Stephen P</creatorcontrib><creatorcontrib>Morris, Emma C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Yuan</au><au>Xue, Shao-An</au><au>Behboudi, Shahriar</au><au>Mohammad, Goran H</au><au>Pereira, Stephen P</au><au>Morris, Emma C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2017-10-15</date><risdate>2017</risdate><volume>23</volume><issue>20</issue><spage>6178</spage><epage>6189</epage><pages>6178-6189</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer. In this study, we have characterized the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2-restricted peptide, pCEA691-699, isolated from the peripheral T-cell repertoire of pancreatic cancer patients and sought to determine if
PD-L1 and TIM-3 blockade could enhance CTL function.
CD8
T-cell lines were generated from peripheral blood mononuclear cells of 18 HLA-A2
patients with pancreatic cancer and from 15 healthy controls.
peptide-specific responses were evaluated by flow cytometry after staining for intracellular cytokine production and carboxy fluorescein succinimydyl ester cytotoxicity assays using pancreatic cancer cell lines as targets.
Cytokine-secreting functional CEA691-specific CTL lines were successfully generated from 10 of 18 pancreatic cancer patients, with two CTL lines able to recognize and kill both CEA691 peptide-loaded T2 cells and CEA
HLA-A2
pancreatic cancer cell lines. In the presence of
PD-L1 blockade, functional CEA691-specific CD8
T-cell responses, including IFNγ secretion and proliferation, were enhanced, and this effect was more pronounced on Ag-specific T cells isolated from tumor draining lymph nodes.
These data demonstrate that CEA691-specific CTL can be readily expanded from the self-restricted T-cell repertoire of pancreatic cancer patients and that their function can be enhanced by PD-L1 blockade.
.</abstract><cop>United States</cop><pub>American Association for Cancer Research Inc</pub><pmid>28710313</pmid><doi>10.1158/1078-0432.CCR-17-1185</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Antigens Antineoplastic Agents, Immunological - pharmacology B7-H1 Antigen - metabolism Biomarkers, Tumor Biotechnology Cancer Carcinoembryonic antigen Carcinoembryonic Antigen - immunology CD8 antigen Cell Line, Tumor Cytokines Cytokines - metabolism Cytometry Cytotoxicity Cytotoxicity, Immunologic - drug effects Cytotoxicity, Immunologic - immunology Experimental design Female Flow cytometry Fluorescein Hepatitis A Virus Cellular Receptor 2 - antagonists & inhibitors Hepatitis A Virus Cellular Receptor 2 - metabolism Histocompatibility antigen HLA Humans Immunophenotyping Immunotherapy Leukocytes (mononuclear) Lymph nodes Lymphocytes Lymphocytes T Male Middle Aged Neoplasm Staging Pancreatic cancer Pancreatic Neoplasms - immunology Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Patients PD-1 protein PD-L1 protein Peptides Peripheral blood mononuclear cells Programmed Cell Death 1 Receptor - metabolism Signal Transduction T cell receptors T-Cell Antigen Receptor Specificity - immunology T-Lymphocyte Subsets - drug effects T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism T-Lymphocytes, Cytotoxic - drug effects T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - metabolism Toxicity Tumor cell lines γ-Interferon |
| title | Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients |
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