Department of Pathology, Tongji Hospital, Tongji University, Shanghai, China.
Department of Pathology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Front Immunol. 2024 Mar 12;15:1384548. doi: 10.3389/fimmu.2024.1384548. eCollection 2024.
Colorectal cancer (CRC) presents a substantial challenge characterized by unacceptably high mortality and morbidity, primarily attributed to delayed diagnosis and reliance on palliative care. The immune response of the host plays a pivotal role in carcinogenesis, with IL-38 emerging as a potential protective factor in CRC. However, the precise involvement of IL-38 among various leucocytes, its interactions with PD-1/PD-L1, and its impact on metastasis require further elucidation.
Our investigation revealed a significant correlation between IL-38 expression and metastasis, particularly concerning survival and interactions among diverse leucocytes within draining lymph nodes. In the mesentery lymph nodes, we observed an inverse correlation between IL-38 expression and stages of lymph node invasions (TNM), invasion depth, distance, and differentiation. This aligns with an overall survival advantage associated with higher IL-38 expression in CRC patients' nodes compared to lower levels, as well as elevated IL-38 expression on CD4 or CD8 cells. Notably, a distinct subset of patients characterized by IL-38/PD-1 expression exhibited superior survival outcomes compared to other combinations.
Our findings demonstrate that IL-38 expression in colorectal regional nodes from CRC patients is inversely correlated with PD-1/PD-L1 but positively correlated with infiltrating CD4 or CD8 lymphocytes. The combined assessment of IL-38 and PD-1 expression in colorectal regional nodes emerges as a promising biomarker for predicting the prognosis of CRC.
结直肠癌(CRC)是一个重大挑战,其特点是死亡率和发病率高得令人无法接受,主要归因于诊断延迟和依赖姑息治疗。宿主的免疫反应在癌变中起着关键作用,IL-38 是 CRC 中一种潜在的保护因素。然而,IL-38 在各种白细胞中的确切作用、它与 PD-1/PD-L1 的相互作用及其对转移的影响仍需进一步阐明。
我们的研究表明,IL-38 的表达与转移之间存在显著相关性,特别是在与引流淋巴结中各种白细胞的生存和相互作用有关。在肠系膜淋巴结中,我们观察到 IL-38 表达与淋巴结侵袭(TNM)、浸润深度、距离和分化的阶段呈负相关。这与 CRC 患者淋巴结中 IL-38 表达水平较高与较低水平相比总体生存优势一致,以及 CD4 或 CD8 细胞上的 IL-38 表达升高。值得注意的是,与其他组合相比,IL-38/PD-1 表达的特定患者亚组表现出更好的生存结果。
我们的研究结果表明,CRC 患者结直肠区域淋巴结中 IL-38 的表达与 PD-1/PD-L1 呈负相关,但与浸润性 CD4 或 CD8 淋巴细胞呈正相关。联合评估结直肠区域淋巴结中的 IL-38 和 PD-1 表达可能成为预测 CRC 预后的有前途的生物标志物。