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Overexpressed in numerous cancers, DDRs participate in tumorigenesis, tumor growth, dissemination, and metastasis. Immune checkpoint inhibitors (ICIs) have demonstrated low response rates in tumors such as head and neck cancer and pancreatic cancer, possibly due to the insufficient presence of effector T cells and the abundant collagen fibers in the tumor microenvironment. Recently, several studies indicate that DDRs account for ICIs resistance. For instance, DDR1 can prevent the anti\u2010tumor immune responses via mediating the rearrangement of collagen fibers, increasing the secretion of interleukin\u201018 (IL\u201018) as well as facilitating the formation of neutrophil extracellular traps (NETs). DDR2 may participate in the establishment of immunosuppressive tumor microenvironment by recruiting myeloid\u2010derived suppressor cells (MDSCs) and promoting the M2 polarization of macrophages. Notably, the interaction between collagens and immune cells also acts as a pivotal role in mediating tumor immune escape. Targeting DDRs and upstream regulators including collagen has been reported to significantly restore the antitumor immunity or inhibit tumor development, such as utilizing DDR1 inhibitors via AI screening from FDA\u2010approved therapeutics or natural products, and strategies for collagen synthesis inhibition or collagen degradation. However, the above approaches are largely limited to preclinical studies and still warrant further validation in clinical trials. Based on the current evidences, DDRs serve as promising targets for improving the efficacy of ICIs against cancers; more studies are anticipated to reveal unclarified mechanisms of DDRs in regulating anti\u2010tumor immunity.<\/jats:p>","DOI":"10.1002\/ijc.70398","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:17:27Z","timestamp":1772993847000},"page":"3080-3090","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The critical role of discoidin domain receptors in the regulation of anti\u2010tumor immune responses"],"prefix":"10.1002","volume":"158","author":[{"given":"Sixin","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University  Chengdu 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