{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:57:32Z","timestamp":1791262652434,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major global health concern, with a higher incidence in men than in women. In the era of immunotherapy, understanding sex\u2010based immunological differences is crucial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\/Patients<\/jats:title>\n                    <jats:p>This study investigated sex\u2010specific differences in anti\u2010tumor immunity in HCC through immune profiling of liver biopsies and blood samples. A prospective cohort of 101 patients was analyzed by multiparametric flow cytometry to assess lymphocyte populations and immune checkpoint molecule expression on tumoral and nontumoral biopsies and blood samples. Then, a retrospective cohort of 56 patients was analyzed for circulating immune markers and functional assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our findings indicate that while overall intrahepatic immune composition was similar between sexes, female patients exhibited higher intra\u2010tumoral PD\u20101\n                      <jats:sup>high+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell frequency compared to men (13.3%\u2009\u00b1\u20092.6% vs. 6.5%\u2009\u00b1\u20090.7%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0127), suggesting greater T cell exhaustion. Additionally, NK cells expressing CTLA\u20104 and ICOS were more frequent in females. Circulating immune profiles also differed, with female patients showing increased CTLA\u20104\n                      <jats:sup>+<\/jats:sup>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0005 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0164) and reduced IFN\u03b3 expression, mainly in central memory CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings highlight the importance of considering sex\u2010related differences in the context of immunotherapy for HCC and underline the need for further investigation in larger cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72297","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T06:33:01Z","timestamp":1789799581000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Analysis of the Immune Profiles of Women and Men With Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2553-5971","authenticated-orcid":false,"given":"Zuzana","family":"Macek Jilkova","sequence":"first","affiliation":[{"name":"Univ. Grenoble Alpes  Grenoble France"},{"name":"Institute for Advanced Biosciences, Research Center UGA\/Inserm U 1209\/CNRS 5309  Grenoble France"},{"name":"Hepato\u2010Gastroenterology and Digestive Oncology Department CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Ghelfi","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes  Grenoble France"},{"name":"Institute for Advanced Biosciences, Research Center UGA\/Inserm U 1209\/CNRS 5309  Grenoble France"},{"name":"Department of Radiology CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucile","family":"Dumolard","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes  Grenoble France"},{"name":"Institute for Advanced Biosciences, Research Center UGA\/Inserm U 1209\/CNRS 5309  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Sinniger","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes  Grenoble France"},{"name":"Institute for Advanced Biosciences, Research Center UGA\/Inserm U 1209\/CNRS 5309  Grenoble France"},{"name":"Hepato\u2010Gastroenterology and Digestive Oncology Department CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour El Houda","family":"Mehdi","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes  Grenoble France"},{"name":"Institute for Advanced Biosciences, Research Center UGA\/Inserm U 1209\/CNRS 5309  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9004-256X","authenticated-orcid":false,"given":"Christian","family":"Sengel","sequence":"additional","affiliation":[{"name":"Department of Radiology CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9785-8729","authenticated-orcid":false,"given":"Yann","family":"Teyssier","sequence":"additional","affiliation":[{"name":"Department of Radiology CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6115-8512","authenticated-orcid":false,"given":"Charlotte","family":"Costentin","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes  Grenoble France"},{"name":"Institute for Advanced Biosciences, Research Center UGA\/Inserm U 1209\/CNRS 5309  Grenoble France"},{"name":"Hepato\u2010Gastroenterology and Digestive Oncology Department CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0928-0048","authenticated-orcid":false,"given":"Thomas","family":"Decaens","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes  Grenoble France"},{"name":"Institute for Advanced Biosciences, Research Center UGA\/Inserm U 1209\/CNRS 5309  Grenoble France"},{"name":"Hepato\u2010Gastroenterology and Digestive Oncology Department CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32723"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00825-3"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-020-00291-x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djae191"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology12070984"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1140485"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-1117"},{"key":"e_1_2_12_9_1","first-page":"53","article-title":"Sex Differences in Hepatocellular Carcinoma","volume":"10","author":"Ho J. 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