Optogenetic engineered macrophages for light-induced M1 polarization and enhanced chemo-immunotherapy in melanoma models

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Kunqian He , Hao Jiang , Wanqi Zhang , Nan Yang , Shuangjiang Li , Yanguo Wang , Junbo Zhang , Xinying Li , Liuchang Tan , Guihong Yang , Hongli Li , Yuangang Lu
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引用次数: 0

Abstract

Macrophage-based adoptive cell therapies hold promise for solid tumors, but spatiotemporally controlling macrophage polarization within the immunosuppressive tumor microenvironment remains challenging. Here, we aimed to validate an optogenetic strategy using the LOV2-STIM1 system to achieve light-induced, sustained M1 polarization of macrophages. Upon blue light stimulation, engineered macrophages robustly exhibited M1 phenotypes, suppressed melanoma cell proliferation, migration, and invasion in vitro, and recapitulated the antitumor functions of M1 macrophages. Notably, combining light-activated engineered macrophages with temozolomide in melanoma models resulted in synergistic inhibition of tumor growth. This synergy is accompanied by a profound remodeling of the tumor immune microenvironment, characterized by M1-driven reversal of chemoresistance and enhanced infiltration of cytotoxic CD8+ T cells. Our findings establish a proof-of-concept for optogenetic regulation of macrophage polarization and demonstrate its feasibility for enhancing antitumor effects and chemosensitivity in melanoma models, providing a promising and controllable platform for macrophage-based immunotherapy.
光基因工程巨噬细胞用于黑色素瘤模型的光诱导M1极化和增强化学免疫治疗。
基于巨噬细胞的过继细胞疗法有望治疗实体瘤,但在免疫抑制的肿瘤微环境中时空控制巨噬细胞极化仍然具有挑战性。在这里,我们旨在验证利用LOV2-STIM1系统实现巨噬细胞光诱导、持续M1极化的光遗传学策略。在蓝光刺激下,工程巨噬细胞明显表现出M1表型,在体外抑制黑色素瘤细胞的增殖、迁移和侵袭,重现了M1巨噬细胞的抗肿瘤功能。值得注意的是,在黑色素瘤模型中,将光活化工程巨噬细胞与替莫唑胺联合使用可协同抑制肿瘤生长。这种协同作用伴随着肿瘤免疫微环境的深刻重塑,其特征是m1驱动的化疗耐药逆转和细胞毒性CD8+ T细胞浸润增强。我们的研究结果为光遗传学调控巨噬细胞极化建立了概念验证,并证明了其在黑色素瘤模型中增强抗肿瘤作用和化疗敏感性的可行性,为巨噬细胞免疫治疗提供了一个有前景的可控平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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