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Immunol."],"abstract":"<jats:p>Cancer immunotherapy has demonstrated remarkable efficacy across multiple tumor types. Despite their significant clinical benefits, most patients with solid tumors remain refractory to immunotherapy, and initial responders frequently develop acquired resistance. Tumor plasticity is a key driver of resistance to cancer immunotherapy. In this review, we discuss how epigenetic and metabolic plasticity of tumor contributes to immunotherapy resistance and highlight emerging strategies targeting these programs to overcome resistance and improve clinical outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1968997","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:32:09Z","timestamp":1791196329000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic and metabolic plasticity of tumor cells in immunotherapy resistance"],"prefix":"10.3389","volume":"17","author":[{"given":"Jee-Eun","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital","place":["Hong Kong, Hong Kong SAR, China"]},{"name":"Centre for Oncology and Immunology, Hong Kong Science Park","place":["Hong Kong, Hong Kong SAR, 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