{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:24:50Z","timestamp":1783013090741,"version":"3.54.6"},"reference-count":3,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The investigation by Wu et\u00a0al. into the synergistic application of interleukin\u201015 (IL\u201015) and thymosin 1 (T1) marks a pivotal advancement in addressing CD8+ T\u2010cell immunosenescence within the hepatocellular carcinoma (HCC) microenvironment. By utilizing a clinically relevant aged orthotopic model, the authors demonstrate that a dual\u2010compartment strategy\u2014leveraging central replenishment and peripheral rescue\u2014significantly attenuates tumor progression. However, a critical reappraisal of the functional data suggests that the observed therapeutic benefit may stem from a \u201cstrategic change of the guard\u201d rather than a literal phenotypic reversal of senescent cells. Specifically, the persistently low Granzyme B expression within terminally differentiated CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD28\n                    <jats:sup>\u2212<\/jats:sup>\n                    populations across treatment arms implies that efficacy is primarily driven by T1\u2010mediated thymic output and the IL\u201015\u2010induced expansion of newly recruited, non\u2010senescent effectors. Furthermore, the mechanistic focus on PI3K\/AKT pathway suppression as a \u201ctherapeutic reset\u201d introduces a significant metabolic paradox. Although effective in breaking the cycle of chronic tonic signaling that defines the senescent state, systemic attenuation of this axis risks blunting the acute metabolic fitness required for robust immune responses in an already fragile aged population. This commentary emphasizes that distinguishing between population replacement and cellular rejuvenation is paramount for predicting long\u2010term durability. Future clinical translations should look beyond the CD8+ compartment to integrate the pleiotropic effects of these agents on the broader immune landscape to ensure both oncological efficacy and systemic immunological safety.\n                  <\/jats:p>","DOI":"10.1111\/jgh.70471","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:43:47Z","timestamp":1780055027000},"page":"2212-2213","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regarding IL\u201015 Plus Thymosin \u03b11 Reduces Senescent Hepatic CD8+ T Cells in Hepatocellular Carcinoma via PI3K\/AKT Suppression"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5217-0755","authenticated-orcid":false,"given":"Ilker","family":"Sengul","sequence":"first","affiliation":[{"name":"Thyroidology Unit, Faculty of Medicine Giresun University  Giresun Turkey"},{"name":"Division of Endocrine Surgery, Faculty of Medicine Giresun University  Giresun Turkey"},{"name":"Department of General Surgery, Faculty of Medicine Giresun University  Giresun Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0416-0621","authenticated-orcid":false,"given":"Demet","family":"Sengul","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine Giresun University  Giresun Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"e_1_2_1_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.70359"},{"issue":"3","key":"e_1_2_1_7_3_1","first-page":"365","article-title":"Ischemic Preconditioning and Postconditioning in Cardiovascular Surgery","volume":"32","author":"Sengul I.","year":"2010","journal-title":"Cumhuriyet Medical Journal"},{"key":"e_1_2_1_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kjms.2012.08.021"}],"container-title":["Journal of Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.70471","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jgh.70471","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.70471","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:03:06Z","timestamp":1783011786000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jgh.70471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":3,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/jgh.70471"],"URL":"https:\/\/doi.org\/10.1111\/jgh.70471","archive":["Portico"],"relation":{},"ISSN":["0815-9319","1440-1746"],"issn-type":[{"value":"0815-9319","type":"print"},{"value":"1440-1746","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"assertion":[{"value":"2026-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}