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Downregulation of major histocompatibility complex class I (MHC-I) on tumor cells is a common immune evasion strategy that profoundly shapes TAM composition and function. Conversely, TAMs reciprocally modulate tumor MHC-I expression. This review provides an overview of the verified and hypothetical mechanisms of bidirectional regulatory interactions between MHC-I on tumor cells and TAMs. Since these interactions likely differ between tumors with reversible and irreversible MHC-I downregulation, their potential significance in tumor immunotherapy should be assessed separately for each MHC-I reduction mechanism.<\/jats:p>","DOI":"10.1093\/cei\/uxag047","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T11:55:19Z","timestamp":1786190119000},"source":"Crossref","is-referenced-by-count":0,"title":["Macrophages in tumors with downregulated MHC-I expression: emerging therapeutic opportunities and translational challenges"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-8357","authenticated-orcid":false,"given":"Adrianna","family":"Piatakova","sequence":"first","affiliation":[{"name":"Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV , Vestec ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0366-4932","authenticated-orcid":false,"given":"Michal","family":"Smahel","sequence":"additional","affiliation":[{"name":"Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV , Vestec ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"2026081810515953200_uxag047-B1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41392-025-02325-5","article-title":"Dual roles and therapeutic targeting of tumor-associated macrophages in tumor microenvironments","volume":"10","author":"Xu","year":"2025","journal-title":"Sig Transduct Target 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