{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T11:34:25Z","timestamp":1794569665385,"version":"4.9.1"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T00:00:00Z","timestamp":1696204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"the National Cancer Institute of the National Institutes of Health","award":["P50CA217691"],"award-info":[{"award-number":["P50CA217691"]}]},{"name":"the Integrated Cellular Imaging Microscopy Core","award":["2P30CA138282-04"],"award-info":[{"award-number":["2P30CA138282-04"]}]},{"name":"the Cancer Tissue and Pathology shared resource of the Winship Cancer Institue of Emory University","award":["P30CA13829"],"award-info":[{"award-number":["P30CA13829"]}],"id":[{"id":"https:\/\/ror.org\/02gars961","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the Monell Foundation","award":["-"],"award-info":[{"award-number":["-"]}]},{"DOI":"10.13039\/501100003725","name":"the National Research Foundation of Korea grant","doi-asserted-by":"crossref","award":["RS-2023-00211426"],"award-info":[{"award-number":["RS-2023-00211426"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the National Cancer Center grant","award":["NCC-19112605"],"award-info":[{"award-number":["NCC-19112605"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,10,10]]},"abstract":"<jats:p>\n                    CD8 T cells play an essential role in antitumor immunity and chronic viral infections. Recent findings have delineated the differentiation pathway of CD8 T cells in accordance with the progenitor-progeny relationship of TCF1\n                    <jats:sup>+<\/jats:sup>\n                    stem-like and Tim-3\n                    <jats:sup>+<\/jats:sup>\n                    TCF1\n                    <jats:sup>\u2212<\/jats:sup>\n                    more differentiated T cells. Here, we investigated the characteristics of stem-like and differentiated CD8 T cells isolated from several murine tumor models and human lung cancer samples in terms of phenotypic and transcriptional features as well as their location compared to virus-specific CD8 T cells in the chronically lymphocytic choriomeningitis virus (LCMV)-infected mice. We found that CD8 tumor-infiltrating lymphocytes (TILs) in both murine and human tumors exhibited overall similar phenotypic and transcriptional characteristics compared to corresponding subsets in the spleen of chronically infected mice. Moreover, stem-like CD8 TILs exclusively responded and produced effector-like progeny CD8 T cells in vivo after antigenic restimulation, confirming their lineage relationship and the proliferative potential of stem-like CD8 TILs. Most importantly, similar to the preferential localization of PD-1\n                    <jats:sup>+<\/jats:sup>\n                    stem-like CD8 T cells in T cell zones of the spleen during chronic LCMV infection, we found that the PD-1\n                    <jats:sup>+<\/jats:sup>\n                    stem-like CD8 TILs in lung cancer samples are preferentially located not in the tumor parenchyma but in tertiary lymphoid structures (TLSs). The stem-like CD8 T cells are present in TLSs located within and at the periphery of the tumor, as well as in TLSs closely adjacent to the tumor parenchyma. These findings suggest that TLSs provide a protective niche to support the quiescence and maintenance of stem-like CD8 T cells in the tumor.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2221985120","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T15:09:50Z","timestamp":1696259390000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":97,"title":["Characteristics and anatomic location of PD-1\n                    <sup>+<\/sup>\n                    TCF1\n                    <sup>+<\/sup>\n                    stem-like CD8 T cells in chronic viral infection and cancer"],"prefix":"10.1073","volume":"120","author":[{"given":"Se Jin","family":"Im","sequence":"first","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Department of Immunology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C.","family":"Obeng","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5650-1563","authenticated-orcid":false,"given":"Tahseen H.","family":"Nasti","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"McManus","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9230-9501","authenticated-orcid":false,"given":"Alice O.","family":"Kamphorst","sequence":"additional","affiliation":[{"name":"Department of Immunology and Immunotherapy, Lipschultz Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029"},{"name":"Department of Oncological Sciences, Lipschultz Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivaram","family":"Gunisetty","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Prokhnevska","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Department of Urology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer W.","family":"Carlisle","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel L.","family":"Sica","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas E.","family":"Cardozo","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Eisnstein, Sao Paulo 05652, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 N. 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