Heras-Murillo Ignacio, Mañanes Diego, Munné Pablo, Núñez Vanessa, Herrera Jessica, Catalá-Montoro Mauro, Alvarez Maite, Del Pozo Miguel A, Melero Ignacio, Wculek Stefanie K, Sancho David
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Universidad Autónoma de Madrid, Escuela de Doctorado, Madrid, Spain.
Nat Commun. 2025 Apr 9;16(1):3369. doi: 10.1038/s41467-025-58289-1.
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.
树突状细胞(DC)癌症疫苗的潜力尚未得到充分发挥。对于不同天然DC亚群引发的抗癌免疫反应的确切性质及其在预防术后肿瘤复发中的相关性,我们了解甚少。在此,我们使用用肿瘤细胞裂解物脉冲处理的小鼠脾脏常规DC1(cDC1)或cDC2来制备DC疫苗。基于cDC1的疫苗接种可诱导更强的效应和记忆性CD4和CD8抗肿瘤T细胞反应,从而更好地控制接受治疗性或预防性治疗的肿瘤。使用肿瘤复发的实验模型,我们发现辅助性或新辅助性cDC1疫苗接种可改善抗肿瘤免疫记忆,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。这转化为对肿瘤复发的完全预防。此外,cDC1s丰度的升高与CD4 Trm的存在呈正相关,且二者均与人类乳腺癌和黑色素瘤患者的生存率提高相关。我们的研究结果表明,基于cDC1的疫苗接种在诱导免疫记忆和预防癌症复发方面表现出色。
J Immunother Cancer. 2019-4-8
Nat Rev Clin Oncol. 2024-4
Cancer Cell. 2023-3-13
Nat Rev Immunol. 2023-8