RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune checkpoint inhibitors in melanoma: mechanisms, immune cell interactions, and the tumour microenvironment.
Immune checkpoint inhibitors in melanoma: mechanisms, immune cell interactions, and the tumour microenvironment.
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黑色素瘤是一种起源于黑色素细胞的高度侵袭性和转移性恶性肿瘤,全球发病率不断上升,对患者预后构成重大挑战。晚期黑色素瘤的传统疗法疗效有限。近年来,免疫检查点抑制剂(ICIs)的出现显著改变了这一局面,通过阻断免疫检查点蛋白与其配体之间的相互作用,重新激活机体的抗肿瘤免疫反应,展现出显著的治疗效果。
然而,部分患者对ICIs无应答或产生耐药性,提示治疗反应涉及肿瘤、免疫细胞与肿瘤微环境之间的复杂相互作用。本综述全面总结了ICIs的作用机制,深入探讨了多种免疫细胞(包括T细胞、NK细胞、巨噬细胞、辅助性T细胞、树突状细胞和B细胞)及肿瘤微环境(TME)的作用,并探讨了它们对ICI疗效的影响。
进一步区分了ICBs在不同疾病阶段(原发、辅助、新辅助和转移性)的应用,并重点阐述了皮肤特异性免疫细胞(如TRM、朗格汉斯细胞)和微环境组分(如皮肤微生物组)的作用。本综述聚焦于ICIs在黑色素瘤治疗中的机制,探索免疫细胞与皮肤微环境在黑色素瘤发生发展中的相互作用及其对ICI疗效的影响,旨在为优化黑色素瘤治疗中的免疫治疗策略提供新的见解和理论基础。
Melanoma is a highly aggressive and metastatic malignant tumor originating from melanocytes, with globally rising incidence rates that pose significant challenges to patient prognosis. Traditional therapies for advanced melanoma have limited efficacy. In recent years, the emergence of immune checkpoint inhibitors (ICIs) has significantly altered this landscape by reactivating the body's antitumor immune response through blocking interactions between immune checkpoint proteins and their ligands, demonstrating remarkable therapeutic outcomes.
However, some patients do not respond to ICIs or develop resistance, indicating that treatment responses involve complex interactions between tumors, immune cells, and the tumor microenvironment. This review comprehensively summarizes the mechanisms of ICIs, delves into the roles of various immune cells (including T cells, NK cells, macrophages, T helper cells, dendritic cells, and B cells) and the tumor microenvironment (TME), and explores their impact on ICI efficacy.
It further distinguishes the application of ICBs across different disease stages (primary, adjuvant, neoadjuvant, and metastatic) and highlights the role of skin-specific immune cells (e. g. , TRM, Langerhans cells) and microenvironmental components (e. g. , skin microbiome).
This review focuses on the mechanisms of ICIs in melanoma therapy, exploring the interactions between immune cells and the skin microenvironment in melanoma development and their impact on ICI efficacy. It aims to provide new insights and theoretical foundations for optimizing immunotherapy strategies in melanoma treatment.
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