Dang Jie, He Zhiyun, Cui Xiang, Fan Jingchun, Hambly David J, Hambly Brett D, Li Xun, Bao Shisan
Child and Adolescent Health Management Center, Lanzhou University Second Hospital, Lanzhou, China.
Department of General Surgery, Lanzhou University First Hospital, Lanzhou, China.
Front Med (Lausanne). 2022 Feb 2;9:811025. doi: 10.3389/fmed.2022.811025. eCollection 2022.
Colorectal cancer (CRC) is a major killer. Dysregulation of IL-37 and IL-38, both anti-inflammatory cytokines, is observed in auto-immune diseases. The precise regulatory mechanisms of IL-37/IL-38 during the development of CRC remains unclear, but chronic intestinal inflammation is involved in the carcinogenesis of CRC. Constitutive production of colonic IL-37 and IL-38 is substantially reduced in CRC, consistent with an inverse correlation with CRC differentiation. Reduced colonic IL-37 and IL-38 is relating to CRC invasion and distant metastasis, suggesting a protective role for IL-38 within the tumor micro-environment. IL-38 is reduced in right-sided CRC compared to left-sided CRC, which is in line with multiple risk factors for right-sided CRC, including the embryonic development of the colon, and genetic differences in CRC between these two sides. Finally, colonic IL-37 and tumor associated neutrophils (TAN) seem to be independent biomarkers of prognostic value, whereas colonic IL-38 seems to be a reliable and independent biomarker in predicting the 5-year survival post-surgery in CRC. However, there is room for improvement in available studies, including the extension of these studies to different regions/countries incorporating different races, evaluation of the role of multi-drug resistance, and different subsets of CRC. It would be useful to determine the kinetics of circulating IL-38 and its relationship with drug resistance/targeted therapy. The measurement of colonic IL-38 at the molecular and cellular level is required to explore the contribution of IL-38 pathways during the development of CRC. These approaches could provide insight for the development of personalized medicine.
结直肠癌（CRC）是主要的致死病因。在自身免疫性疾病中观察到抗炎细胞因子白细胞介素-37（IL-37）和白细胞介素-38（IL-38）的失调。CRC发生发展过程中IL-37/IL-38的确切调控机制尚不清楚，但慢性肠道炎症参与了CRC的致癌过程。CRC中结肠IL-37和IL-38的组成性产生显著减少，这与CRC分化呈负相关。结肠IL-37和IL-38减少与CRC侵袭和远处转移有关，提示IL-38在肿瘤微环境中具有保护作用。与左侧CRC相比，右侧CRC中IL-38减少，这与右侧CRC的多种危险因素一致，包括结肠的胚胎发育以及两侧CRC的基因差异。最后，结肠IL-37和肿瘤相关中性粒细胞（TAN）似乎是具有预后价值的独立生物标志物，而结肠IL-38似乎是预测CRC术后5年生存率的可靠且独立的生物标志物。然而，现有研究仍有改进空间，包括将这些研究扩展到纳入不同种族的不同地区/国家、评估多药耐药性的作用以及CRC的不同亚组。确定循环IL-38的动力学及其与耐药性/靶向治疗的关系将很有用。需要在分子和细胞水平上测量结肠IL-38，以探索IL-38通路在CRC发生发展过程中的作用。这些方法可为个性化医疗的发展提供见解。
