{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:37:34Z","timestamp":1781649454241,"version":"3.54.5"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Multiple primary malignancies (MPMs) are increasingly recognized, yet the impact of immune checkpoint inhibitors (ICIs) on the evolution of metachronous tumors remains poorly understood. Here, we report a rare case of metachronous triple primary malignancies\u2014lung squamous cell carcinoma, gastric adenocarcinoma, and hepatocellular carcinoma (HCC)\u2014in a 68-year-old male with chronic HBV infection and a history of heavy tobacco and alcohol use. Notably, while receiving the PD-1 inhibitor sintilimab for gastric adenocarcinoma, a previously stable hepatic nodule underwent rapid malignant transformation into histologically confirmed HCC. This paradoxical progression occurred despite the patient achieving a partial response in the gastric lesion and sustained remission of the lung malignancy. Given the patient\u2019s high-risk hepatic background, this case raises the hypothesis that ICIs may inadvertently disrupt local immune tolerance in a predisposed \u201cpro-oncogenic soil, \u201d potentially catalyzing the transition of dormant pre-neoplastic lesions. This report underscores the need for rigorous baseline liver assessment and close radiological surveillance in high-risk patients undergoing immunotherapy, and highlights the importance of further research into the organ-specific effects of ICIs.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1831238","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:37:25Z","timestamp":1777613845000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Anti-PD-1 therapy as a catalyst for the rapid transformation of a hepatic nodule into HCC: a \u201csoil and seed\u201d paradox in metachronous triple primary malignancies?"],"prefix":"10.3389","volume":"17","author":[{"given":"Xian","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Oncology, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dehua","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Oncology, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boan","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Suining Central Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, Suining Central Hospital","place":["Suining, Sichuan, 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