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Thus, there is a great need for the identification of reliable predictive biomarkers for response and toxicity. The cytokine MIF (macrophage migration inhibitory factor) and its cognate receptor CD74 are intimately connected with cancer progression and have previously been proposed as prognostic biomarkers for patient outcome in various cancers, including solid tumors such as malignant melanoma. Here, we assess their potential as predictive biomarkers for response to ICB therapy and irAE development. We provide a brief overview of their function and roles in the context of cancer and autoimmune disease. We also review the evidence showing that MIF and CD74 may be of use as predictive biomarkers of patient response to ICB therapy and irAE development. We also highlight that careful consideration is required when assessing the potential of serum MIF levels as a biomarker due to its reported circadian expression in human plasma. Finally, we suggest future directions for the establishment of MIF and CD74 as predictive biomarkers for ICB therapy and irAE development to guide further research in this field.<\/jats:p>","DOI":"10.3390\/cancers16091773","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T13:27:00Z","timestamp":1715002020000},"page":"1773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["MIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3202-1012","authenticated-orcid":false,"given":"Rosalyn M.","family":"Fey","sequence":"first","affiliation":[{"name":"Department of Dermatology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-7575","authenticated-orcid":false,"given":"Thuy T.","family":"Tran","sequence":"additional","affiliation":[{"name":"Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur A.","family":"Vandenbark","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research, R&D-31, VA Portland Health Care System, Portland, OR 97239, USA"},{"name":"Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2191-4085","authenticated-orcid":false,"given":"Rajan P.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Cancer Early Detection Advanced Research Center (CEDAR), Portland, OR 97239, USA"},{"name":"Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA"},{"name":"Operative Care Division, U.S. Department of Veterans Affairs Portland Health Care System, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alturki, N.A. 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