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.
可溶性CD26（sCD26）是一种具有二肽基肽酶（DPP4）活性的糖蛋白，有助于结直肠癌和晚期腺瘤的早期诊断，并已在多种其他癌症和疾病中开展研究，包括用于预后评估。该领域最新研究证实，尽管并非全部，但大多数血清/血浆sCD26与炎症相关。目前正在研究不同免疫细胞释放和/或分泌sCD26的机制，且血液DPP4活性水平与蛋白滴度相关性较弱。该酶的主要底物包括参与免疫细胞迁移的关键趋化因子，可溶性及细胞表面CD26均可结合腺苷脱氨酶（ADA）——一种参与免疫抑制性胞外腺苷代谢的酶。值得注意的是，存在CD26高表达的T细胞亚群，在小鼠肿瘤模型中，肿瘤浸润淋巴细胞中CD26+细胞比例升高与肿瘤消退相关。我们将sCD26作为结直肠癌根治性切除术后随访的生物标志物，用于早期检测肿瘤复发。在类风湿关节炎中，也观察到包括Ig-CTLA4在内的不同生物改善病情抗风湿药治疗后的变化。近期一项人源化抗CD26抗体癌症免疫治疗的I期试验后，血清可溶性CD26/DPP4滴度变化被提议作为潜在的预后生物标志物。我们认为，除已作为免疫检查点免疫治疗参考指标的CRP等经典炎症生物标志物外，动态监测sCD26/DPP4变化可能提示治疗各阶段的耐药性或治疗反应。鉴于表达CD26的肿瘤细胞也能产生sCD26，本文还探讨了区分免疫系统与非免疫系统来源sCD26的可能性。
肿瘤(癌症)患者之家