CD26/Dipeptidyl Peptidase IV and Its Multiple Biological Functions

Our plain-English summary of CD26/Dipeptidyl Peptidase IV and Its Multiple Biological Functions, by K. Pan, K. Ohnuma, C. Morimoto, et al (Curēus, 2021).

The study

• Authors: K. Pan, K. Ohnuma, C. Morimoto, N.H. Dang
• Journal: Curēus
• Published: 2021;13(2):e13495
• Type of article: Review
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright © 2021, Pan et al.

In plain English

This article was a narrative review of published research, not a new study. It covered CD26, also called dipeptidyl peptidase IV (DPPIV), a protein on the surface of many cell types. The authors reviewed its reported roles in the immune system, diabetes, cancer, and infections including MERS and COVID-19. The article did not discuss asbestos. In its section on malignant pleural mesothelioma, it described earlier studies by other researchers. In one study of 79 patients, 73.4% of tumors showed CD26 on the cell surface. Most epithelioid and biphasic tumors carried it, but sarcomatoid tumors did not. Among patients given chemotherapy, CD26 expression was linked with longer mean survival (18.6 versus 10.7 months). The review also described two early (phase I) trials of an anti-CD26 antibody called YS110. One included 33 patients with CD26-positive cancers, 22 of them with malignant mesothelioma. In the other, nine Japanese patients with advanced mesothelioma took part, and four of seven had stable disease while one had a partial response. The authors concluded that YS110 gave what they called promising results in advanced pleural mesothelioma that had progressed after chemotherapy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative literature review
• Who was studied: No new population was studied. The review drew on published laboratory, animal and human studies of CD26/DPPIV, including studies of patients with malignant pleural mesothelioma.
• Exposure: Not an asbestos exposure study. The subject is the molecule CD26/DPPIV and treatments aimed at it: DPPIV-inhibitor drugs (gliptins) and anti-CD26 monoclonal antibodies such as YS110.
• Main results:
  • The review reported a cited study (reference 24) of 79 patients with malignant pleural mesothelioma in which 73.4% of tumors showed CD26 on the cell surface.
  • In the same cited study, most epithelioid and biphasic mesotheliomas expressed surface CD26, but sarcomatoid mesotheliomas did not.
  • In the cited work, CD26 surface expression was linked with longer mean survival among mesothelioma patients who received chemotherapy: 18.6 versus 10.7 months, p = 0.0083.
  • The review described a cited first-in-human phase I trial of YS110 (reference 25) in 33 heavily pretreated patients with CD26-positive cancers, 22 of whom had malignant mesothelioma. Stable disease was seen in half of the patients at 43 days, prolonged stabilization in seven of 13 patients with stable disease, and a median progression-free survival of 33 weeks.
  • In a cited phase I trial (reference 26), nine Japanese patients with advanced malignant pleural mesothelioma received YS110 at two, four or six mg/kg. Four of seven patients had stable disease and one had a partial response.
  • In that Japanese trial, seven of the nine patients had grade three or four adverse events, most often a decreased lymphocyte count. None had a dose-limiting toxicity.
• The authors' conclusion: The authors concluded that YS110 yielded what they called promising antineoplastic outcomes in advanced malignant pleural mesothelioma that had progressed on several chemotherapy agents. They said this suggests a possibly better-tolerated and possibly more effective treatment in certain cancers.
• Limitations the authors state:
  • The authors stated that more experimental and clinical data are needed on whether DPPIV inhibitors reduce viral entry or inflammation in COVID-19. This is a gap in the evidence they reviewed, not a limitation of the review itself.

Topics

Medical terms in this study, explained in our Lexicon: Glycoprotein, Carcinogenesis, Pleural Mesothelioma, Carcinoma, Biomarker, Monoclonal Antibody, Neoplasm.

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