MIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy

Rosalyn M Fey; Rebecca A Nichols; Thuy T Tran; Arthur A Vandenbark; Rajan P Kulkarni

doi:10.3390/cancers16091773

MIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy

Cancers (Basel). 2024 May 4;16(9):1773. doi: 10.3390/cancers16091773.

Authors

Rosalyn M Fey¹, Rebecca A Nichols¹, Thuy T Tran², Arthur A Vandenbark^{3

4

5}, Rajan P Kulkarni^{1

6

7

8}

Affiliations

¹ Department of Dermatology, Oregon Health & Science University, Portland, OR 97239, USA.
² Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA.
³ Neuroimmunology Research, R&D-31, VA Portland Health Care System, Portland, OR 97239, USA.
⁴ Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
⁵ Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
⁶ Cancer Early Detection Advanced Research Center (CEDAR), Portland, OR 97239, USA.
⁷ Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
⁸ Operative Care Division, U.S. Department of Veterans Affairs Portland Health Care System, Portland, OR 97239, USA.

Abstract

Immune checkpoint blockade (ICB) therapy is used to treat a wide range of cancers; however, some patients are at risk of developing treatment resistance and/or immune-related adverse events (irAEs). 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.

Keywords: CD74; autoimmune disease; biomarkers; cancer; immune checkpoint blockade (ICB); immune-related adverse events (irAEs); macrophage migration inhibitory factor (MIF).

Publication types

Review

Grants and funding

This research was funded by the following sources: The American Cancer Society, grant no. 129523-MRSG-16-029-01-DDC. The Department of Defense (DOD), grant numbers: W81XWH-17-1-0514 and W81XWH-17-1-0098. OHSU Cancer Early Detection Advanced Research Center (CEDAR), the ACED alliance award number 19P0023, and the Kuni Foundation Discovery Grant (all to RPK). AAV acknowledges the following: NIH NINDS the National Institute of Allergy and Infectious Diseases award 2R42AI122574, Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Merit Review Award 2I01 BX000226, BLR&D Merit Review for Pre-IND studies of Drugs and Biologics Award 5I01 BX005112, and Senior Research Career Scientist Award 1IK6BX004209. The contents of this article do not necessarily represent the views of the Department of Veterans Affairs or the US Government.