IL-10在肿瘤中的双向调控作用：核心机制、临床前研究及临床转化

Bidirectional regulation and research progress of IL-10 in tumors: core mechanisms, preclinical studies, and clinical translation

摘要:

白细胞介素10（IL-10）作为多功能细胞因子，在肿瘤免疫微环境中呈现显著的双向调控特性，既可通 过构建免疫抑制微环境驱动肿瘤进展，亦可激活抗肿瘤免疫抑制肿瘤生长。这一效应转向由分泌来源、产生方式、 受体状态、肿瘤特征四大核心变量协同决定。其促瘤效应主要体现为通过下调抗原呈递功能构建肿瘤免疫抑制微 环境，同时激活肿瘤细胞自分泌存活信号，促进肿瘤侵袭与转移；抑瘤效应则通过促进肿瘤内CD8 + T细胞的浸润， 增强 CD8 + T细胞、NK细胞等效应免疫细胞的杀伤功能，重塑肿瘤免疫微环境发挥肿瘤抑制作用。本文系统梳理 IL-10在肿瘤中双向调控的核心机制，总结基于 IL-10的激动与拮抗策略相关临床前研究进展，并分析其临床转化 现状、核心瓶颈及优化方向，为IL-10相关疗法的临床开发提供参考。

Abstract:

Interleukin-10 (IL-10), as a multifunctional cytokine, exhibits remarkable bidirectional regulatory properties within the tumor immune microenvironment. It can both drive tumor progression by establishing an immunosuppressive microenvironment and suppress tumor growth by activating antitumor immunity. This functional duality is orchestrated by four core variables: the cellular source, mode of production, receptor status, and tumor-specific characteristics. Its protumor effect is mainly manifested in the establishment of an immunosuppressive tumor microenvironment by down-regulating antigen presentation, as well as the activation of autocrine survival signals of tumor cells to promote tumor invasion and metastasis. In contrast, its antitumor effect exerts tumor-suppressive activity by facilitating the infiltration of CD8+ T cells into the tumor, enhancing the cytotoxic functions of effector immune cells such as CD8+ T cells and natural killer (NK) cells, and remodeling the tumor immune microenvironment. This review systematically elucidates the core mechanisms underlying the bidirectional regulation of IL-10 in tumors, summarizes the advances in preclinical studies on IL-10-based agonistic and antagonistic strategies, and analyzes the current status, key bottlenecks and optimization directions of its clinical translation, thereby providing a reference for the clinical development of IL-10-related therapeutic regimens.