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癌症相关成纤维细胞与树突状细胞之间的相互作用:对肿瘤免疫的影响

Interplay between cancer-associated fibroblasts and dendritic cells: implications for tumor immunity.

作者信息

Mentucci Fátima María, Ferrara María Gracia, Ercole Agustina, Rumie Vittar Natalia Belén, Lamberti María Julia

机构信息

Instituto de Biotecnología Ambiental y Salud (INBIAS UNRC CONICET)-UNRC, Río Cuarto, Córdoba, Argentina.

Departamento de Biología Molecular, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Río Cuarto, Córdoba, Argentina.

出版信息

Front Immunol. 2025 May 16;16:1515390. doi: 10.3389/fimmu.2025.1515390. eCollection 2025.

Abstract

The tumor microenvironment (TME) plays a critical role in cancer progression, with cancer-associated fibroblasts (CAFs) emerging as key players in immune evasion. This review explores the complex interactions between CAFs and dendritic cells (DCs), essential antigen-presenting cells that activate immune responses. CAFs impair DC maturation and function by secreting cytokines, chemokines, and growth factors, reducing their ability to present antigens and stimulate T cells, thus promoting an immunosuppressive environment favorable to tumor growth. Additionally, CAFs contribute to the differentiation of tolerogenic DCs, fostering regulatory T cells (Tregs) that further suppress antitumor immunity. This review examines the molecular mechanisms underlying CAF-DC crosstalk and discusses potential therapeutic strategies aimed at restoring DC functionality. Targeting the CAF-driven immunosuppressive network offers promising opportunities to enhance the efficacy of DC-based vaccines and immunotherapies, paving the way for improved cancer treatment outcomes.

摘要

肿瘤微环境(TME)在癌症进展中起关键作用,癌症相关成纤维细胞(CAF)成为免疫逃逸的关键参与者。本综述探讨了CAF与树突状细胞(DC)之间的复杂相互作用,DC是激活免疫反应的重要抗原呈递细胞。CAF通过分泌细胞因子、趋化因子和生长因子来损害DC的成熟和功能,降低其呈递抗原和刺激T细胞的能力,从而促进有利于肿瘤生长的免疫抑制环境。此外,CAF有助于诱导耐受性DC的分化,促进调节性T细胞(Treg)的生成,而Treg会进一步抑制抗肿瘤免疫。本综述研究了CAF-DC相互作用的分子机制,并讨论了旨在恢复DC功能的潜在治疗策略。靶向CAF驱动的免疫抑制网络为提高基于DC的疫苗和免疫疗法的疗效提供了有前景的机会,为改善癌症治疗结果铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9647/12122520/74f87938743b/fimmu-16-1515390-g001.jpg

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