文章目录

细胞因子武装的树突状细胞祖细胞用于抗原不可知的癌症免疫治疗

原文发布日期：2023-11-23

英文摘要：

摘要翻译：

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文章：

细胞因子武装的树突状细胞祖细胞用于抗原不可知的癌症免疫治疗

Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy

原文发布日期：2023-11-23

英文摘要：

Dendritic cells (DCs) are antigen-presenting myeloid cells that regulate T cell activation, trafficking and function. Monocyte-derived DCs pulsed with tumor antigens have been tested extensively for therapeutic vaccination in cancer, with mixed clinical results. Here, we present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 and FLT3L. Cytokine-armed DCPs differentiated into conventional type-I DCs (cDC1) and suppressed tumor growth, including melanoma and autochthonous liver models, without the need for antigen loading or myeloablative host conditioning. Tumor response involved synergy between IL-12 and FLT3L and was associated with natural killer and T cell infiltration and activation, M1-like macrophage programming and ischemic tumor necrosis. Antitumor immunity was dependent on endogenous cDC1 expansion and interferon-γ signaling but did not require CD8+ T cell cytotoxicity. Cytokine-armed DCPs synergized effectively with anti-GD2 chimeric-antigen receptor (CAR) T cells in eradicating intracranial gliomas in mice, illustrating their potential in combination therapies.

摘要翻译：

树突状细胞（DCs）是一种抗原呈递的髓系细胞，调控T细胞的激活、转运及功能。单核细胞前体生成的树突状细胞脉冲肿瘤抗原被广泛用于癌症治疗性疫苗研究中，但疗效参差不齐。在此处，我们介绍了一种基于小鼠或人类祖粒状细胞前体（DCPs）构建的细胞疗法平台，这些祖粒状细胞经过修饰后会产生两种促免疫因子：IL-12和FLT3L。靶向抗原的祖粒状细胞分化为常规型I树突状细胞（cDC1），这种细胞能够抑制肿瘤生长，包括黑色素瘤及原发性肝癌模型。这一过程无需加载抗原或进行非激进的宿主条件诱导。T细胞反应涉及IL-12和FLT3L之间的协同作用，并与自然杀伤细胞、T细胞渗透及激活、M1类巨噬细胞编程及缺血性肿瘤坏死有关。抗肿瘤免疫反应依赖于内源性cDC1的增殖以及IFN-γ信号传导，但无需CD8+ T细胞杀伤性功能。靶向抗原的祖粒状细胞与anti-GD2杂交抗原受体（CAR）T细胞协同作用，在小鼠去势抵抗性胶质母细胞瘤模型中有效消除肿瘤，表明其在联合治疗中的潜力。