The Interplay Between Neutrophils and CD8 + T Cells Improves Survival in Human Colorectal Cancer
Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer. Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes, and functional features of colorectal cancer-infiltrating CD66b neutrophils...
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| Veröffentlicht in: | Clinical cancer research 2017-07, Vol.23 (14), p.3847-3858 |
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| creator | Governa, Valeria Trella, Emanuele Mele, Valentina Tornillo, Luigi Amicarella, Francesca Cremonesi, Eleonora Muraro, Manuele Giuseppe Xu, Hui Droeser, Raoul Däster, Silvio R Bolli, Martin Rosso, Raffaele Oertli, Daniel Eppenberger-Castori, Serenella Terracciano, Luigi M Iezzi, Giandomenica Spagnoli, Giulio C |
| description | Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer. Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes, and functional features of colorectal cancer-infiltrating CD66b
neutrophils and their crosstalk with CD8
T cells.
CD66b
and CD8
cell infiltration was analyzed by IHC on a tissue microarray including >650 evaluable colorectal cancer samples. Phenotypic profiles of tissue-infiltrating and peripheral blood CD66b
cells were evaluated by flow cytometry. CD66b
/CD8
cells crosstalk was investigated by
experiments.
CD66b
cell infiltration in colorectal cancer is significantly associated with increased survival. Interestingly, neutrophils frequently colocalize with CD8
T cells in colorectal cancer. Functional studies indicate that although neutrophils are devoid of direct antitumor potential, coculture with peripheral blood or tumor-associated neutrophils (TAN) enhances CD8
T-cell activation, proliferation, and cytokine release induced by suboptimal concentrations of anti-CD3 mAb. Moreover, under optimal activation conditions, CD8
cell stimulation in the presence of CD66b
cells results in increasing numbers of cells expressing CD45RO/CD62L "central memory" phenotype. Importantly, combined tumor infiltration by CD66b
and CD8
T lymphocytes is associated with significantly better prognosis, as compared with CD8
T-cell infiltration alone.
Neutrophils enhance the responsiveness of CD8
T cells to T-cell receptor triggering. Accordingly, infiltration by neutrophils enhances the prognostic significance of colorectal cancer infiltration by CD8
T cells, suggesting that they might effectively promote antitumor immunity.
. |
| doi_str_mv | 10.1158/1078-0432.CCR-16-2047 |
| format | Article |
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neutrophils and their crosstalk with CD8
T cells.
CD66b
and CD8
cell infiltration was analyzed by IHC on a tissue microarray including >650 evaluable colorectal cancer samples. Phenotypic profiles of tissue-infiltrating and peripheral blood CD66b
cells were evaluated by flow cytometry. CD66b
/CD8
cells crosstalk was investigated by
experiments.
CD66b
cell infiltration in colorectal cancer is significantly associated with increased survival. Interestingly, neutrophils frequently colocalize with CD8
T cells in colorectal cancer. Functional studies indicate that although neutrophils are devoid of direct antitumor potential, coculture with peripheral blood or tumor-associated neutrophils (TAN) enhances CD8
T-cell activation, proliferation, and cytokine release induced by suboptimal concentrations of anti-CD3 mAb. Moreover, under optimal activation conditions, CD8
cell stimulation in the presence of CD66b
cells results in increasing numbers of cells expressing CD45RO/CD62L "central memory" phenotype. Importantly, combined tumor infiltration by CD66b
and CD8
T lymphocytes is associated with significantly better prognosis, as compared with CD8
T-cell infiltration alone.
Neutrophils enhance the responsiveness of CD8
T cells to T-cell receptor triggering. Accordingly, infiltration by neutrophils enhances the prognostic significance of colorectal cancer infiltration by CD8
T cells, suggesting that they might effectively promote antitumor immunity.
.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-16-2047</identifier><identifier>PMID: 28108544</identifier><language>eng</language><publisher>United States: American Association for Cancer Research Inc</publisher><subject>Aged ; Antigens, CD - genetics ; Antigens, CD - immunology ; Antitumor activity ; Cancer ; CD3 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - pathology ; Cell activation ; Cell Adhesion Molecules - genetics ; Cell Adhesion Molecules - immunology ; Cell Proliferation - genetics ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - immunology ; Colorectal Neoplasms - pathology ; Crosstalk ; Cytometry ; Experimental design ; Female ; Flow cytometry ; GPI-Linked Proteins - genetics ; GPI-Linked Proteins - immunology ; Humans ; Immune system ; Immunity ; Infiltration ; Innate immunity ; Kaplan-Meier Estimate ; L-selectin ; Leukocytes (neutrophilic) ; Lymphocytes ; Lymphocytes T ; Male ; Medical prognosis ; Metastases ; Middle Aged ; Neoplastic Stem Cells - immunology ; Neoplastic Stem Cells - pathology ; Neutrophils ; Neutrophils - immunology ; Neutrophils - pathology ; Peripheral blood ; Prognosis ; Survival ; T cell receptors ; T-Lymphocyte Subsets - immunology ; Tissue Array Analysis</subject><ispartof>Clinical cancer research, 2017-07, Vol.23 (14), p.3847-3858</ispartof><rights>2017 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research Inc Jul 15, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-5d7b23f7c0350e6057269b982e62083de95b47ed13d7c2faa54f9b072e1857633</citedby><cites>FETCH-LOGICAL-c488t-5d7b23f7c0350e6057269b982e62083de95b47ed13d7c2faa54f9b072e1857633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28108544$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Governa, Valeria</creatorcontrib><creatorcontrib>Trella, Emanuele</creatorcontrib><creatorcontrib>Mele, Valentina</creatorcontrib><creatorcontrib>Tornillo, Luigi</creatorcontrib><creatorcontrib>Amicarella, Francesca</creatorcontrib><creatorcontrib>Cremonesi, Eleonora</creatorcontrib><creatorcontrib>Muraro, Manuele Giuseppe</creatorcontrib><creatorcontrib>Xu, Hui</creatorcontrib><creatorcontrib>Droeser, Raoul</creatorcontrib><creatorcontrib>Däster, Silvio R</creatorcontrib><creatorcontrib>Bolli, Martin</creatorcontrib><creatorcontrib>Rosso, Raffaele</creatorcontrib><creatorcontrib>Oertli, Daniel</creatorcontrib><creatorcontrib>Eppenberger-Castori, Serenella</creatorcontrib><creatorcontrib>Terracciano, Luigi M</creatorcontrib><creatorcontrib>Iezzi, Giandomenica</creatorcontrib><creatorcontrib>Spagnoli, Giulio C</creatorcontrib><title>The Interplay Between Neutrophils and CD8 + T Cells Improves Survival in Human Colorectal Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer. Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes, and functional features of colorectal cancer-infiltrating CD66b
neutrophils and their crosstalk with CD8
T cells.
CD66b
and CD8
cell infiltration was analyzed by IHC on a tissue microarray including >650 evaluable colorectal cancer samples. Phenotypic profiles of tissue-infiltrating and peripheral blood CD66b
cells were evaluated by flow cytometry. CD66b
/CD8
cells crosstalk was investigated by
experiments.
CD66b
cell infiltration in colorectal cancer is significantly associated with increased survival. Interestingly, neutrophils frequently colocalize with CD8
T cells in colorectal cancer. Functional studies indicate that although neutrophils are devoid of direct antitumor potential, coculture with peripheral blood or tumor-associated neutrophils (TAN) enhances CD8
T-cell activation, proliferation, and cytokine release induced by suboptimal concentrations of anti-CD3 mAb. Moreover, under optimal activation conditions, CD8
cell stimulation in the presence of CD66b
cells results in increasing numbers of cells expressing CD45RO/CD62L "central memory" phenotype. Importantly, combined tumor infiltration by CD66b
and CD8
T lymphocytes is associated with significantly better prognosis, as compared with CD8
T-cell infiltration alone.
Neutrophils enhance the responsiveness of CD8
T cells to T-cell receptor triggering. Accordingly, infiltration by neutrophils enhances the prognostic significance of colorectal cancer infiltration by CD8
T cells, suggesting that they might effectively promote antitumor immunity.
.</description><subject>Aged</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - immunology</subject><subject>Antitumor activity</subject><subject>Cancer</subject><subject>CD3 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - pathology</subject><subject>Cell activation</subject><subject>Cell Adhesion Molecules - genetics</subject><subject>Cell Adhesion Molecules - immunology</subject><subject>Cell Proliferation - genetics</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - immunology</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Crosstalk</subject><subject>Cytometry</subject><subject>Experimental design</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>GPI-Linked Proteins - genetics</subject><subject>GPI-Linked Proteins - immunology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Infiltration</subject><subject>Innate immunity</subject><subject>Kaplan-Meier Estimate</subject><subject>L-selectin</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Neoplastic Stem Cells - immunology</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Neutrophils</subject><subject>Neutrophils - immunology</subject><subject>Neutrophils - pathology</subject><subject>Peripheral blood</subject><subject>Prognosis</subject><subject>Survival</subject><subject>T cell receptors</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>Tissue Array Analysis</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>eNpdkVtL5EAQhRtx8f4TlAZfBMlsV1_SnUfNrjogK7izz20nqWAkl7E7mWX-vR28PPhURfGd4nAOIafAFgDK_ASmTcKk4Is8f0wgTTiTeoccgFI6ETxVu3H_ZPbJYQgvjIEEJvfIPjfAjJLygDytnpEu-xH9unVbeo3jf8Se_sFp9MP6uWkDdX1F81-GXtIVzbGNl2W39sMGA_07-U2zcS1teno3da6n-dAOHssx3nLXl-iPyY_atQFPPuYR-Xfze5XfJfcPt8v86j4ppTFjoipdcFHrkgnFMGVK8zQrMsMx5cyICjNVSI0ViEqXvHZOyTormOYIRulUiCNy8f43WnudMIy2a0IZ7boehylYMGmMTQHM6Pk39GWYfB_dWciMkKC1yCKl3qnSDyF4rO3aN53zWwvMzhXYOV47x2tjBRZSO1cQdWcf36eiw-pL9Zm5eAOEoX9N</recordid><startdate>20170715</startdate><enddate>20170715</enddate><creator>Governa, Valeria</creator><creator>Trella, Emanuele</creator><creator>Mele, Valentina</creator><creator>Tornillo, Luigi</creator><creator>Amicarella, Francesca</creator><creator>Cremonesi, Eleonora</creator><creator>Muraro, Manuele Giuseppe</creator><creator>Xu, Hui</creator><creator>Droeser, Raoul</creator><creator>Däster, Silvio R</creator><creator>Bolli, Martin</creator><creator>Rosso, Raffaele</creator><creator>Oertli, Daniel</creator><creator>Eppenberger-Castori, Serenella</creator><creator>Terracciano, Luigi M</creator><creator>Iezzi, Giandomenica</creator><creator>Spagnoli, Giulio 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>7X8</scope></search><sort><creationdate>20170715</creationdate><title>The Interplay Between Neutrophils and CD8 + T Cells Improves Survival in Human Colorectal Cancer</title><author>Governa, Valeria ; Trella, Emanuele ; Mele, Valentina ; Tornillo, Luigi ; Amicarella, Francesca ; Cremonesi, Eleonora ; Muraro, Manuele Giuseppe ; Xu, Hui ; Droeser, Raoul ; Däster, Silvio R ; Bolli, Martin ; Rosso, Raffaele ; Oertli, Daniel ; Eppenberger-Castori, Serenella ; Terracciano, Luigi M ; Iezzi, Giandomenica ; Spagnoli, Giulio C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-5d7b23f7c0350e6057269b982e62083de95b47ed13d7c2faa54f9b072e1857633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Antigens, CD - genetics</topic><topic>Antigens, CD - immunology</topic><topic>Antitumor activity</topic><topic>Cancer</topic><topic>CD3 antigen</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - pathology</topic><topic>Cell activation</topic><topic>Cell Adhesion Molecules - genetics</topic><topic>Cell Adhesion Molecules - immunology</topic><topic>Cell Proliferation - genetics</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - immunology</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Crosstalk</topic><topic>Cytometry</topic><topic>Experimental design</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>GPI-Linked Proteins - genetics</topic><topic>GPI-Linked Proteins - immunology</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunity</topic><topic>Infiltration</topic><topic>Innate immunity</topic><topic>Kaplan-Meier Estimate</topic><topic>L-selectin</topic><topic>Leukocytes (neutrophilic)</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Neoplastic Stem Cells - immunology</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Neutrophils</topic><topic>Neutrophils - immunology</topic><topic>Neutrophils - pathology</topic><topic>Peripheral blood</topic><topic>Prognosis</topic><topic>Survival</topic><topic>T cell receptors</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>Tissue Array Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Governa, Valeria</creatorcontrib><creatorcontrib>Trella, Emanuele</creatorcontrib><creatorcontrib>Mele, Valentina</creatorcontrib><creatorcontrib>Tornillo, Luigi</creatorcontrib><creatorcontrib>Amicarella, Francesca</creatorcontrib><creatorcontrib>Cremonesi, Eleonora</creatorcontrib><creatorcontrib>Muraro, Manuele Giuseppe</creatorcontrib><creatorcontrib>Xu, Hui</creatorcontrib><creatorcontrib>Droeser, Raoul</creatorcontrib><creatorcontrib>Däster, Silvio R</creatorcontrib><creatorcontrib>Bolli, Martin</creatorcontrib><creatorcontrib>Rosso, Raffaele</creatorcontrib><creatorcontrib>Oertli, Daniel</creatorcontrib><creatorcontrib>Eppenberger-Castori, Serenella</creatorcontrib><creatorcontrib>Terracciano, Luigi M</creatorcontrib><creatorcontrib>Iezzi, Giandomenica</creatorcontrib><creatorcontrib>Spagnoli, Giulio 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>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Governa, Valeria</au><au>Trella, Emanuele</au><au>Mele, Valentina</au><au>Tornillo, Luigi</au><au>Amicarella, Francesca</au><au>Cremonesi, Eleonora</au><au>Muraro, Manuele Giuseppe</au><au>Xu, Hui</au><au>Droeser, Raoul</au><au>Däster, Silvio R</au><au>Bolli, Martin</au><au>Rosso, Raffaele</au><au>Oertli, Daniel</au><au>Eppenberger-Castori, Serenella</au><au>Terracciano, Luigi M</au><au>Iezzi, Giandomenica</au><au>Spagnoli, Giulio C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Interplay Between Neutrophils and CD8 + T Cells Improves Survival in Human Colorectal Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2017-07-15</date><risdate>2017</risdate><volume>23</volume><issue>14</issue><spage>3847</spage><epage>3858</epage><pages>3847-3858</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer. Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes, and functional features of colorectal cancer-infiltrating CD66b
neutrophils and their crosstalk with CD8
T cells.
CD66b
and CD8
cell infiltration was analyzed by IHC on a tissue microarray including >650 evaluable colorectal cancer samples. Phenotypic profiles of tissue-infiltrating and peripheral blood CD66b
cells were evaluated by flow cytometry. CD66b
/CD8
cells crosstalk was investigated by
experiments.
CD66b
cell infiltration in colorectal cancer is significantly associated with increased survival. Interestingly, neutrophils frequently colocalize with CD8
T cells in colorectal cancer. Functional studies indicate that although neutrophils are devoid of direct antitumor potential, coculture with peripheral blood or tumor-associated neutrophils (TAN) enhances CD8
T-cell activation, proliferation, and cytokine release induced by suboptimal concentrations of anti-CD3 mAb. Moreover, under optimal activation conditions, CD8
cell stimulation in the presence of CD66b
cells results in increasing numbers of cells expressing CD45RO/CD62L "central memory" phenotype. Importantly, combined tumor infiltration by CD66b
and CD8
T lymphocytes is associated with significantly better prognosis, as compared with CD8
T-cell infiltration alone.
Neutrophils enhance the responsiveness of CD8
T cells to T-cell receptor triggering. Accordingly, infiltration by neutrophils enhances the prognostic significance of colorectal cancer infiltration by CD8
T cells, suggesting that they might effectively promote antitumor immunity.
.</abstract><cop>United States</cop><pub>American Association for Cancer Research Inc</pub><pmid>28108544</pmid><doi>10.1158/1078-0432.CCR-16-2047</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2017-07, Vol.23 (14), p.3847-3858 |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Aged Antigens, CD - genetics Antigens, CD - immunology Antitumor activity Cancer CD3 antigen CD8 antigen CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - pathology Cell activation Cell Adhesion Molecules - genetics Cell Adhesion Molecules - immunology Cell Proliferation - genetics Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - immunology Colorectal Neoplasms - pathology Crosstalk Cytometry Experimental design Female Flow cytometry GPI-Linked Proteins - genetics GPI-Linked Proteins - immunology Humans Immune system Immunity Infiltration Innate immunity Kaplan-Meier Estimate L-selectin Leukocytes (neutrophilic) Lymphocytes Lymphocytes T Male Medical prognosis Metastases Middle Aged Neoplastic Stem Cells - immunology Neoplastic Stem Cells - pathology Neutrophils Neutrophils - immunology Neutrophils - pathology Peripheral blood Prognosis Survival T cell receptors T-Lymphocyte Subsets - immunology Tissue Array Analysis |
| title | The Interplay Between Neutrophils and CD8 + T Cells Improves Survival in Human Colorectal Cancer |
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