Immunotherapy with conventional type-1 dendritic cells induces immune memory and limits tumor relapse
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<sup>+</sup> and CD8<sup>+</sup> 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<sup>+</sup> tissue resident memory (Trm) and CD8<sup>+</sup> memory T cells. This translates into complete prevention of tumor relapses. Moreover, elevated abundance of cDC1s positively correlates with CD4<sup>+</sup> 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.
Authors
- Diego Mañanes (ORCID: https://orcid.org/0000-0001-7247-6794)
- Vanessa Núñez (ORCID: https://orcid.org/0000-0002-7473-1514)
- Jessica Herrera (ORCID: https://orcid.org/0000-0001-7091-296X)
- Stefanie K. Wculek (ORCID: https://orcid.org/0000-0001-5565-8561)
- Ignacio Melero (ORCID: https://orcid.org/0000-0002-1360-348X)
- Miguel Á. del Pozo (ORCID: https://orcid.org/0000-0001-9077-391X)
- David Sancho (ORCID: https://orcid.org/0000-0003-2890-3984)
- Ignacio Heras‐Murillo (ORCID: https://orcid.org/0000-0002-8797-8786)
- Maite Álvarez (ORCID: https://orcid.org/0000-0002-5969-9181)
- Pablo Munné
- Mauro Catalá-Montoro
Institutions
- Churchill Hospital (GB)
- Spanish National Centre for Cardiovascular Research (ES)
- Navarre Institute of Health Research (ES)
- Institute for Research in Biomedicine (ES)
- Spanish National Centre for Cardiovascular Research (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Universidad Autónoma de Madrid (ES)
- Universidad de Navarra (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-09
- DOI
- https://doi.org/10.1038/s41467-025-58289-1
- Citations
- 17
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 13.56
Funders
- Institute for Research in Biomedicine
- Comunidad de Madrid
- Ministerio de Ciencia, Innovación y Universidades
- Centres de Recerca de Catalunya
- European Commission
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- Centro Nacional de Investigaciones Cardiovasculares
- Fundación Fero
- Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona
- HORIZON EUROPE Framework Programme
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación