Abstract
CD26/Dipeptidyl peptidase IV (DPPIV) is a cell surface glycoprotein with numerous roles including glucose metabolism, immunomodulation, and tumorigenesis. CD26/DPPIV is well recognized in diabetes, with DPPIV inhibitors being a class of oral hypoglycemic drugs called gliptins that are commonly used to treat type two diabetes mellitus. Recent work also indicated a potential role for CD26 in infectious diseases, including COVID-19, and immune-mediated disorders such as rheumatoid arthritis, inflammatory bowel disease, and graft-versus-host disease.In cancer, CD26/DPPIV expression has been characterized in numerous tumors such as hematologic malignancies, malignant pleural mesothelioma (MPM), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), gastrointestinal stromal tumor (GIST), and prostate, lung, colorectal, and ovarian (PLCO) cancer. Hence, CD26 has been frequently studied as a tumor biomarker and therapeutic target. CD26/DPPIV-targeted therapies have been evaluated in various cancers, including the use of anti-CD26 monoclonal antibodies as anticancer treatment in selected neoplasms.This review highlights our current understanding of the role of CD26 in cancer, diabetes, immune-mediated diseases, and infectious diseases. Enhanced understanding of CD26 biology and function may lead to novel therapeutic approaches in multiple human diseases.
Highlights
BackgroundCD26/Dipeptidyl peptidase IV (DPPIV) is a cell surface glycoprotein that is commonly expressed in many cell types and has numerous biological functions
DPPIV inhibitor sitagliptin reducing the rate of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem-cell transplants (HSCT) suggests an important role in immunosuppression and clinical outcomes of immune-mediated disorders
The administration of the humanized anti-CD26 mAb YS110 yielded promising antineoplastic outcomes in advanced malignant pleural mesothelioma (MPM) that previously progressed on numerous chemotherapy agents, suggesting a more well-tolerated and possibly more effective treatment potential in certain cancers
Summary
CD26/Dipeptidyl peptidase IV (DPPIV) is a cell surface glycoprotein that is commonly expressed in many cell types and has numerous biological functions. Studies have suggested the role of DPPIV inhibitors in endothelial growth by inducing endothelial cell proliferation through the activation of TNF-a or IL-1B. Russo et al found decreased DPPIV mRNA and protein levels in patients with castrate-resistant prostate cancer, and DPPIV inhibition with sitagliptin enhanced prostate cancer xenografts growth after castration These results suggest that DPPIV may play a role in androgen receptor-regulated tumor suppression, and DPPIV inhibition facilitates growth factor activity and tumor growth [31]. The humanized anti-CD26 mAb YS110 exhibited tolerable safety profiles in a phase I clinical trial involving patients with CD26-expressing malignancies, as discussed earlier [20,25] These findings suggest the potential of anti-CD26 mAbs as a novel therapeutic approach in MERS-CoV-mediated infection. There is currently no published experimental data showing that DPPIV inhibitors decrease binding and viral entry
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