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Open AccessReview
Soluble CD26: From Suggested Biomarker for Cancer Diagnosis to Plausible Marker for Dynamic Monitoring of Immunotherapy
by
Martin Kotrulev
Martin Kotrulev 1,2
,
Iria Gomez-Touriño
Iria Gomez-Touriño
Dr. Iria Gomez-Tourino has been an Associate Professor at USC since 2020, and group leader of the to [...]
Dr. Iria Gomez-Tourino has been an Associate Professor at USC since 2020, and group leader of the Immunity and Small Molecules Lab. She has been awarded several fellowships and awards, amounting to more than 1,580,000€, including two prestigious Marie Sklodowska-Curie Individual fellowships (King’s College London, UK, 2013-2015, and USC, Spain, 2018-2020) and more recently the Career Development Award of the Juvenile Diabetes Research Foundation (2023-2028). The latter is aimed at fostering the career of exceptionally promising researchers in the Type 1 Diabetes field, and only three researchers receive this award yearly around the globe. 67% of her publications are in D1 journals, this being the case for her last four articles (Nature Communications, Diabetologia, FASEB Journal, and Nature Immunology). Dr. Gomez is also the inventor of 3 patents, a European Union Expert Evaluator, and an elected member of the Board of Directors of the Spanish Society of Immunology (2022-2026). Her main research interests include the identification and characterization of novel anti-inflammatory small molecules for the treatment of autoimmune diseases, and the study of mechanisms of autoreactivity underlying these pathologies.
1,2,3 and
Oscar J. Cordero
Oscar J. Cordero 2,3,*
1
Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
2
Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
3
Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
*
Author to whom correspondence should be addressed.
Submission received: 9 April 2024
/
Revised: 25 June 2024
/
Accepted: 27 June 2024
/
Published: 30 June 2024
Simple Summary
Prognostic markers have become a promising tool for predicting response to a certain treatment and qualifying patients for a certain therapy; however, it is important to consider that they generally describe a probabilistic scenario. For instance, the analysis of programmed death ligand 1 expression on tumor cells or tumor mutational burden is commonly employed as a biomarker with relative predictive value for immunotherapy efficacy in non-small-cell lung cancer (NSCLC) patients. Cutting-edge techniques, such as next-generation sequencing of tumor tissue and flow cytometry analysis of lymphocyte subpopulations in the peripheral blood of patients, are used with the aim of increasing the predictive value, avoiding statistical weakness and discovering algorithms based on many biomarkers. To resolve the issues posed by these novel techniques, dynamic monitoring of biomarker changes can indicate resistance or response to immunotherapy during different points of the treatment. Hence, clinicians can flexibly modify the therapy course for the benefit of the patient, improving response rates, efficiency in laboratory routines, and the economic cost of the technique. Immune checkpoint immunotherapy alters the local (solid tumor infiltration) and systemic balance among several immune system cell populations. The usefulness of immune-cell-related soluble CD26 and its DPP4 activity in immunotherapy monitoring is discussed.
Abstract
Soluble CD26 (sCD26), a glycoprotein with dipeptidyl peptidase (DPP4) enzymatic activity, can contribute to early diagnosis of colorectal cancer and advanced adenomas and has been studied, including for prognostic purposes, across various other types of cancer and disease. The latest research in this field has confirmed that most, though not all, serum/plasma sCD26 is related to inflammation. The shedding and/or secretion of sCD26 from different immune cells are being investigated, and blood DPP4 activity levels do not correlate very strongly with protein titers. Some of the main substrates of this enzyme are key chemokines involved in immune cell migration, and both soluble and cell-surface CD26 can bind adenosine deaminase (ADA), an enzyme involved in the metabolism of immunosuppressor extracellular adenosine. Of note, there are T cells enriched in CD26 expression and, in mice tumor models, tumor infiltrating lymphocytes exhibited heightened percentages of CD26+ correlating with tumor regression. We employed sCD26 as a biomarker in the follow-up after curative resection of colorectal cancer for the early detection of tumor recurrence. Changes after treatment with different biological disease-modifying antirheumatic drugs, including Ig-CTLA4, were also observed in rheumatoid arthritis. Serum soluble CD26/DPP4 titer variation has recently been proposed as a potential prognostic biomarker after a phase I trial in cancer immunotherapy with a humanized anti-CD26 antibody. We propose that dynamic monitoring of sCD26/DPP4 changes, in addition to well-known inflammatory biomarkers such as CRP already in use as informative for immune checkpoint immunotherapy, may indicate resistance or response during the successive steps of the treatment. As tumor cells expressing CD26 can also produce sCD26, the possibility of sorting immune- from non-immune-system-originated sCD26 is discussed.
Share and Cite
MDPI and ACS Style
Kotrulev, M.; Gomez-Touriño, I.; Cordero, O.J.
Soluble CD26: From Suggested Biomarker for Cancer Diagnosis to Plausible Marker for Dynamic Monitoring of Immunotherapy. Cancers 2024, 16, 2427.
https://doi.org/10.3390/cancers16132427
AMA Style
Kotrulev M, Gomez-Touriño I, Cordero OJ.
Soluble CD26: From Suggested Biomarker for Cancer Diagnosis to Plausible Marker for Dynamic Monitoring of Immunotherapy. Cancers. 2024; 16(13):2427.
https://doi.org/10.3390/cancers16132427
Chicago/Turabian Style
Kotrulev, Martin, Iria Gomez-Touriño, and Oscar J. Cordero.
2024. "Soluble CD26: From Suggested Biomarker for Cancer Diagnosis to Plausible Marker for Dynamic Monitoring of Immunotherapy" Cancers 16, no. 13: 2427.
https://doi.org/10.3390/cancers16132427
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