Self-Maintaining CD103 + Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Enrichment of CD103 tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103 cytotoxic CD8 T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103 CTLs by...
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| Veröffentlicht in: | Cancer immunology research 2020-02, Vol.8 (2), p.203-216 |
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| creator | Abd Hamid, Megat Colin-York, Huw Khalid-Alham, Nasullah Browne, Molly Cerundolo, Lucia Chen, Ji-Li Yao, Xuan Rosendo-Machado, Samara Waugh, Craig Maldonado-Perez, David Bowes, Emma Verrill, Clare Cerundolo, Vincenzo Conlon, Christopher P Fritzsche, Marco Peng, Yanchun Dong, Tao |
| description | Enrichment of CD103
tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103
cytotoxic CD8
T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103
CTLs by assessing T-cell receptor (TCR)-matched CD103
and CD103
cancer-specific CTL immunity
and its immunophenotype
Interestingly, we found that differentiated CD103
cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103
CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103
cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies. |
| doi_str_mv | 10.1158/2326-6066.CIR-19-0554 |
| format | Article |
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tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103
cytotoxic CD8
T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103
CTLs by assessing T-cell receptor (TCR)-matched CD103
and CD103
cancer-specific CTL immunity
and its immunophenotype
Interestingly, we found that differentiated CD103
cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103
CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103
cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies.</description><identifier>ISSN: 2326-6066</identifier><identifier>EISSN: 2326-6074</identifier><identifier>DOI: 10.1158/2326-6066.CIR-19-0554</identifier><identifier>PMID: 31771983</identifier><language>eng</language><publisher>United States</publisher><subject>Antigens, CD - immunology ; Antigens, CD - metabolism ; CD8-Positive T-Lymphocytes - immunology ; Humans ; Immunophenotyping - methods ; Integrin alpha Chains - immunology ; Integrin alpha Chains - metabolism ; Lung Neoplasms - immunology ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Lymphocytes, Tumor-Infiltrating - immunology ; Neoplasms - immunology ; Neoplasms - metabolism ; Neoplasms - pathology ; Prognosis ; Receptors, Antigen, T-Cell - genetics ; Receptors, Antigen, T-Cell - immunology ; T-Lymphocytes, Cytotoxic - immunology ; Transforming Growth Factor beta1 - immunology ; Transforming Growth Factor beta1 - metabolism</subject><ispartof>Cancer immunology research, 2020-02, Vol.8 (2), p.203-216</ispartof><rights>2019 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-de7c7c365d669c8c953990037345d8a0f001826d15939dc5c0395d5093255f033</citedby><cites>FETCH-LOGICAL-c463t-de7c7c365d669c8c953990037345d8a0f001826d15939dc5c0395d5093255f033</cites><orcidid>0000-0003-1479-3251 ; 0000-0002-4905-8233 ; 0000-0002-9072-1367 ; 0000-0002-3531-2464 ; 0000-0003-0040-3793</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31771983$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abd Hamid, Megat</creatorcontrib><creatorcontrib>Colin-York, Huw</creatorcontrib><creatorcontrib>Khalid-Alham, Nasullah</creatorcontrib><creatorcontrib>Browne, Molly</creatorcontrib><creatorcontrib>Cerundolo, Lucia</creatorcontrib><creatorcontrib>Chen, Ji-Li</creatorcontrib><creatorcontrib>Yao, Xuan</creatorcontrib><creatorcontrib>Rosendo-Machado, Samara</creatorcontrib><creatorcontrib>Waugh, Craig</creatorcontrib><creatorcontrib>Maldonado-Perez, David</creatorcontrib><creatorcontrib>Bowes, Emma</creatorcontrib><creatorcontrib>Verrill, Clare</creatorcontrib><creatorcontrib>Cerundolo, Vincenzo</creatorcontrib><creatorcontrib>Conlon, Christopher P</creatorcontrib><creatorcontrib>Fritzsche, Marco</creatorcontrib><creatorcontrib>Peng, Yanchun</creatorcontrib><creatorcontrib>Dong, Tao</creatorcontrib><title>Self-Maintaining CD103 + Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses</title><title>Cancer immunology research</title><addtitle>Cancer Immunol Res</addtitle><description>Enrichment of CD103
tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103
cytotoxic CD8
T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103
CTLs by assessing T-cell receptor (TCR)-matched CD103
and CD103
cancer-specific CTL immunity
and its immunophenotype
Interestingly, we found that differentiated CD103
cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103
CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103
cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies.</description><subject>Antigens, CD - immunology</subject><subject>Antigens, CD - metabolism</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Humans</subject><subject>Immunophenotyping - methods</subject><subject>Integrin alpha Chains - immunology</subject><subject>Integrin alpha Chains - metabolism</subject><subject>Lung Neoplasms - immunology</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Prognosis</subject><subject>Receptors, Antigen, T-Cell - genetics</subject><subject>Receptors, Antigen, T-Cell - immunology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Transforming Growth Factor beta1 - immunology</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><issn>2326-6066</issn><issn>2326-6074</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkW9r2zAQxsVYWUubj7Chl4PhVrIs2XozKF76BzoKaftaaNI50XAkV1LW5tvXJmnoBIeOOz3PHfoh9JWSc0p5c1GyUhSCCHHe3i4KKgvCefUJnezrdfX5kAtxjGYp_SXjaZqK8uoLOma0rqls2Al6foC-K35r5_MYzi9x-4sShn_gVnsDsXgYwLjOGfyIW-j7hC8j4Bu3XPVbPPcQl5DH5ovLK7zQg7O43eaQw-tY1N7iedeBySHiBaQh-ATpDB11uk8w29-n6Olq_tjeFHf317ft5V1hKsFyYaE2tWGCWyGkaYzkTEpCWM0qbhtNOkJoUwpLuWTSGm4Ik9xyIlnJeUcYO0U_d77D5s8arAGfo-7VEN1ax60K2qn_O96t1DL8U7WgtCzFaPB9bxDD8wZSVmuXzPgH2kPYJFUyKqmsZDXN4runJoaUInSHMZSoiZiaaKiJhhqJKSrVRGzUffu440H1zoe9AfVZkIk</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Abd Hamid, Megat</creator><creator>Colin-York, Huw</creator><creator>Khalid-Alham, Nasullah</creator><creator>Browne, Molly</creator><creator>Cerundolo, Lucia</creator><creator>Chen, Ji-Li</creator><creator>Yao, Xuan</creator><creator>Rosendo-Machado, Samara</creator><creator>Waugh, Craig</creator><creator>Maldonado-Perez, David</creator><creator>Bowes, Emma</creator><creator>Verrill, Clare</creator><creator>Cerundolo, Vincenzo</creator><creator>Conlon, Christopher P</creator><creator>Fritzsche, Marco</creator><creator>Peng, Yanchun</creator><creator>Dong, Tao</creator><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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1479-3251</orcidid><orcidid>https://orcid.org/0000-0002-4905-8233</orcidid><orcidid>https://orcid.org/0000-0002-9072-1367</orcidid><orcidid>https://orcid.org/0000-0002-3531-2464</orcidid><orcidid>https://orcid.org/0000-0003-0040-3793</orcidid></search><sort><creationdate>20200201</creationdate><title>Self-Maintaining CD103 + Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses</title><author>Abd Hamid, Megat ; 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tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103
cytotoxic CD8
T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103
CTLs by assessing T-cell receptor (TCR)-matched CD103
and CD103
cancer-specific CTL immunity
and its immunophenotype
Interestingly, we found that differentiated CD103
cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103
CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103
cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies.</abstract><cop>United States</cop><pmid>31771983</pmid><doi>10.1158/2326-6066.CIR-19-0554</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-1479-3251</orcidid><orcidid>https://orcid.org/0000-0002-4905-8233</orcidid><orcidid>https://orcid.org/0000-0002-9072-1367</orcidid><orcidid>https://orcid.org/0000-0002-3531-2464</orcidid><orcidid>https://orcid.org/0000-0003-0040-3793</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Cancer immunology research, 2020-02, Vol.8 (2), p.203-216 |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Antigens, CD - immunology Antigens, CD - metabolism CD8-Positive T-Lymphocytes - immunology Humans Immunophenotyping - methods Integrin alpha Chains - immunology Integrin alpha Chains - metabolism Lung Neoplasms - immunology Lung Neoplasms - metabolism Lung Neoplasms - pathology Lymphocytes, Tumor-Infiltrating - immunology Neoplasms - immunology Neoplasms - metabolism Neoplasms - pathology Prognosis Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - immunology T-Lymphocytes, Cytotoxic - immunology Transforming Growth Factor beta1 - immunology Transforming Growth Factor beta1 - metabolism |
| title | Self-Maintaining CD103 + Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses |
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