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Recent studies have identified a critical component of this ecosystem, double-positive cells (DPCs), which are characterized by simultaneously expressing two markers that are traditionally confined to completely different cell lineages or cell types. In this review, we demonstrated DPCs' formation principles, characterization, classification, functions, and clinical significance. We underscore the multifaceted contributions of DPCs in enhancing tumor invasiveness, facilitating immune evasion, and promoting drug resistance. Understanding the significance of targeting DPCs could open new avenues for therapeutic interventions in cancer treatment.<\/jats:p>","DOI":"10.1515\/jtim-2026-0002","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T10:10:51Z","timestamp":1771323051000},"page":"14-33","source":"Crossref","is-referenced-by-count":1,"title":["The double-positive cells in the tumor microenvironment"],"prefix":"10.1515","volume":"14","author":[{"given":"Xinmiao","family":"Long","sequence":"first","affiliation":[{"name":"The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University\/Hunan Cancer Hospital, Central South University , Changsha , Hunan Province , China"},{"name":"The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University , Changsha , Hunan Province , China"},{"name":"FuRong Laboratory , Changsha , Hunan Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinfei","family":"Du","sequence":"additional","affiliation":[{"name":"The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University\/Hunan Cancer Hospital, Central South University , Changsha , Hunan Province , China"},{"name":"The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University , Changsha , Hunan Province , China"},{"name":"FuRong Laboratory , Changsha , Hunan Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University\/Hunan Cancer Hospital, Central South University , Changsha , Hunan Province , China"},{"name":"The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University , Changsha , Hunan Province , China"},{"name":"FuRong Laboratory , Changsha , Hunan Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Guan","sequence":"additional","affiliation":[{"name":"The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University\/Hunan Cancer Hospital, Central South University , Changsha , Hunan Province , China"},{"name":"The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University , Changsha , Hunan Province , China"},{"name":"FuRong Laboratory , Changsha , Hunan Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyi","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University\/Hunan Cancer Hospital, Central South University , Changsha , Hunan Province , China"},{"name":"The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University , Changsha , Hunan Province , China"},{"name":"FuRong Laboratory , Changsha , Hunan Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xiangya Hospital, Central South University , Changsha , Hunan Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5547-907X","authenticated-orcid":false,"given":"Minghua","family":"Wu","sequence":"additional","affiliation":[{"name":"The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University\/Hunan Cancer Hospital, Central South University , Changsha , Hunan Province , China"},{"name":"The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University , Changsha , Hunan Province , China"},{"name":"FuRong Laboratory , Changsha , Hunan Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"2026021906293004044_j_jtim-2026-0002_ref_001","doi-asserted-by":"crossref","unstructured":"de Visser KE, Joyce JA. 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