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常规 1 型树突状细胞免疫治疗可诱导免疫记忆并限制肿瘤复发

英文原题:Immunotherapy with conventional type-1 dendritic cells induces immune memory and limits tumor relapse.

PubMed 2025/04/09(内容时间) Nat Commun Q1 · IF 18.1(JCR 2025)

研究概要

我们的研究结果表明,基于cDC1的疫苗在诱导免疫记忆和预防癌症复发方面表现出色。

中文摘要

树突状细胞(DC)疫苗抗肿瘤的潜力尚未完全实现。关于不同天然DC亚群所触发的抗肿瘤免疫应答的确切性质及其在预防术后肿瘤复发中的相关性,目前知之甚少。在此,我们使用负载肿瘤细胞裂解物的小鼠脾脏经典DC1(cDC1)或cDC2来制备DC疫苗。基于cDC1的疫苗接种诱导了更强的效应性和记忆性CD4+和CD8+抗肿瘤T细胞应答,从而在治疗性或预防性治疗中均能更好地控制肿瘤。利用肿瘤复发的实验模型,我们表明辅助或新辅助cDC1疫苗接种改善了抗肿瘤免疫记忆,特别是通过增加CD4+组织驻留记忆(Trm)和CD8+记忆T细胞的浸润。这转化为肿瘤复发的完全预防。此外,cDC1的丰度升高与CD4+ Trm的存在正相关,且两者均与人类乳腺癌和黑色素瘤中生存期的改善相关。我们的发现表明,基于cDC1的疫苗在诱导免疫记忆和预防癌症复发方面表现优异。

展开英文摘要原文

The potential of dendritic cell (DC) vaccination against cancer is not fully achieved. Little is known about the precise nature of the anti-cancer immune response triggered by different natural DC subsets and their relevance in preventing postsurgical tumor recurrence. Here, we use mouse splenic conventional DC1s (cDC1s) or cDC2s pulsed with tumor cell lysates to generate DC vaccines. cDC1-based vaccination induces a stronger effector and memory CD4 + and CD8 + anti-tumor T cell response, leading to a better control of tumors treated either therapeutically or prophylactically. Using an experimental model of tumor relapse, we show that adjuvant or neoadjuvant cDC1 vaccination improves anti-tumor immune memory, particularly by increasing the infiltrates of CD4 + tissue resident memory (Trm) and CD8 + memory T cells. This translates into complete prevention of tumor relapses. Moreover, elevated abundance of cDC1s positively correlates with CD4 + Trm presence, and both associate with enhanced survival in human breast cancer and melanoma. Our findings suggest that cDC1-based vaccination excels at immune memory induction and prevention of cancer recurrence.

论文信息

作者
Heras-Murillo I、Mañanes D、Munné P、Núñez V、Herrera J、Catalá-Montoro M、Alvarez M、Del Pozo MA
第一作者单位
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.Spain
通讯作者单位
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. dsancho@cnic.es.Spain
期刊
Nature communications2025 Apr 9
原文标识
PubMed 40204706 · DOI 10.1038/s41467-025-58289-1