{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:18:35Z","timestamp":1793056715402,"version":"4.5.0"},"reference-count":75,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["302962"],"award-info":[{"award-number":["302962"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,6,10]]},"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Melanoma, the most lethal form of skin cancer, has undergone a transformative treatment shift with the advent of checkpoint blockade immunotherapy (CBI). Understanding the intricate network of immune cells infiltrating the tumor and orchestrating the control of melanoma cells and the response to CBI is currently of utmost importance. There is evidence underscoring the significance of tissue-resident memory (TRM) CD8 T cells and classic dendritic cell type 1 (cDC1) in cancer protection. Transcriptomic studies also support the existence of a\n                      <jats:italic>TCF7<\/jats:italic>\n                      + (encoding TCF1) T cell as the most important for immunotherapy response, although uncertainty exists about whether there is a TCF1+TRM\u2009T cell due to evidence indicating TCF1 downregulation for tissue residency activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used multiplexed immunofluorescence and spectral flow cytometry to evaluate TRM CD8 T cells and cDC1 in two melanoma patient cohorts: one immunotherapy-naive and the other receiving immunotherapy. The first cohort was divided between patients free of disease or with metastasis 2 years postdiagnosis while the second between CBI responders and non-responders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our study identifies two CD8+TRM subsets, TCF1+ and TCF1\u2212, correlating with melanoma protection. TCF1+TRM cells show heightened expression of IFN-\u03b3 and Ki67 while TCF1\u2212 TRM cells exhibit increased expression of cytotoxic molecules. In metastatic patients, TRM subsets undergo a shift in marker expression, with the TCF1\u2212 subset displaying increased expression of exhaustion markers. We observed a close spatial correlation between cDC1s and TRMs, with TCF1+TRM\/cDC1 pairs enriched in the stroma and TCF1\u2212 TRM\/cDC1 pairs in tumor areas. Notably, these TCF1\u2212 TRMs express cytotoxic molecules and are associated with apoptotic melanoma cells. Both TCF1+ and TCF1\u2212 TRM subsets, alongside cDC1, prove relevant to CBI response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study supports the importance of TRM CD8 T cells and cDC1 in melanoma protection while also highlighting the existence of functionally distinctive TCF1+ and TCF1\u2212 TRM subsets, both crucial for melanoma control and CBI response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2023-008739","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T15:20:19Z","timestamp":1720192819000},"page":"e008739","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["TCF1-positive and TCF1-negative TRM CD8 T cell subsets and cDC1s orchestrate melanoma protection and immunotherapy response"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2451-0123","authenticated-orcid":false,"given":"Sara\u00ed G","family":"De Le\u00f3n-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Posgrado en Ciencias Biol\u00f3gicas, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico"},{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunoqu\u00edmica, UMAE Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Aguilar-Flores","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, UMAE Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli\u00e1n A","family":"Gaj\u00f3n","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunoqu\u00edmica, UMAE Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico"},{"name":"Posgrado en Ciencias Bioqu\u00edmicas, Facultad de Qu\u00edmica, Universad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Ju\u00e1rez-Flores","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunoqu\u00edmica, UMAE Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico"},{"name":"Unidad de Investigaci\u00f3n en Virolog\u00eda y C\u00e1ncer, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Mantilla","sequence":"additional","affiliation":[{"name":"Servicio de Patolog\u00eda, Hospital de Oncolog\u00eda Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Gerson-Cwilich","sequence":"additional","affiliation":[{"name":"Medical Center American British Cowdray, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Fabi\u00e1n","family":"Mart\u00ednez-Herrera","sequence":"additional","affiliation":[{"name":"Medical Center American British Cowdray, Mexico City, Mexico"},{"name":"Latin American Network for Cancer Research (LAN-CANCER), Lima, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Alejandra","family":"Villegas-Osorno","sequence":"additional","affiliation":[{"name":"Medical Center American British Cowdray, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia T","family":"Guti\u00e9rrez-Quiroz","sequence":"additional","affiliation":[{"name":"UMAE Hospital de Especialidades, Centro M\u00e9dico Nacional General Manuel Avila Camacho, Instituto Mexicano del Seguro Social, Puebla, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Buenaventura-Cisneros","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dica de Alta Especialidad No.25, Instituto Mexicano del Seguro Social, Monterrey, Nuevo Leon, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Alberto","family":"S\u00e1nchez-Prieto","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dica de Alta Especialidad No.25, Instituto Mexicano del Seguro Social, Monterrey, Nuevo Leon, Mexico"},{"name":"Divisi\u00f3n de Atenci\u00f3n Oncol\u00f3gica en Adultos. 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