PDF(Pubmed)
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.
摘要：
可溶性CD26(sCD26),具有二肽基肽酶（DPP4）酶活性的糖蛋白，有助于结直肠癌和晚期腺瘤的早期诊断，包括用于预后目的，跨越各种其他类型的癌症和疾病。这一领域的最新研究证实,虽然不是全部,血清/血浆sCD26与炎症有关。sCD26从不同免疫细胞的脱落和/或分泌正在研究中。和血液DPP4活性水平与蛋白质滴度没有很强的相关性。这种酶的一些主要底物是参与免疫细胞迁移的关键趋化因子，和可溶性和细胞表面CD26可以结合腺苷脱氨酶（ADA），参与免疫抑制剂胞外腺苷代谢的酶。值得注意的是，有富含CD26表达的T细胞，在小鼠肿瘤模型中，肿瘤浸润淋巴细胞显示与肿瘤消退相关的CD26+百分比升高。我们在结直肠癌根治性切除术后的随访中使用sCD26作为生物标志物，以早期检测肿瘤复发。不同生物抗风湿药治疗后的变化，在类风湿性关节炎中也观察到包括Ig-CTLA4。血清可溶性CD26/DPP4滴度变化最近已被提出作为在使用人源化抗CD26抗体的癌症免疫疗法中的I期试验后的潜在预后生物标志物。我们建议动态监测sCD26/DPP4的变化，除了众所周知的炎症生物标志物，如CRP已经用作免疫检查点免疫疗法的信息，可以指示在治疗的连续步骤期间的抗性或响应。由于表达CD26的肿瘤细胞也可以产生sCD26,因此讨论了从非免疫系统起源的sCD26分选免疫的可能性。
