Heras-Murillo, IgnacioMañanes, DiegoMunné, PabloNúñez, VanessaHerrera, JessicaCatalá-Montoro, MauroAlvarez, MaiteDel Pozo, Miguel AMelero, IgnacioWculek, Stefanie KSancho, David2025-07-022025-07-022025-04-09Nat Commun. 2025 Apr 9;16(1):3369.https://hdl.handle.net/20.500.12105/26796We thank the members of the D.S. laboratory and the laboratory of Salvador Iborra for discussions and critical reading of the manuscript. We thank the staff at the CNIC technical units; especially the Animal, Cellomics, and Genomics facilities for technical support. This project was supported by the “la Caixa” Foundation (ID 100010434) INPhINIT Fellowship code LCF/BQ/IN17/11620074 (IHM). IM lab work was supported by Fundación Fero. The SKW laboratory and this work is supported by the IRB Barcelona, the European Union and European Research Council’s Horizon Europe programme (ERC-2023-StG ‘MyTissue’ project number 101117470); by grants RYC2022-036400-I and PID2022-140715OA-I00 from MCIN/AEI/10.13039/501100011033 Agencia Estatal de Investigación, Unión Europea NextGenerationEU/PRTR. IRB Barcelona receives institutional funding from the Spanish Ministry of Science and Innovation through the Centres of Excellence Severo Ochoa Award and from the CERCA Programme / Generalitat de Catalunya. Work in the DS laboratory is funded by the CNIC; by Ministerio de Ciencia, Innovación y Universidades (MICIU) PID2022-137712OB-I00, CPP2021-008310 and CPP2022-009762 MICIU/AEI/10.13039/501100011033 Agencia Estatal de Investigación, Unión Europea NextGenerationEU/PRTR; by Comunidad de Madrid (P2022/BMD-7333 INMUNOVAR-CM); by Scientific Foundation of the Spanish Association Against Cancer (AECC- PRYGN246642SANC); by Worldwide Cancer Research 25-0080; by European Union ERC-2023-PoC; by a research agreement with Inmunotek S.L.; and by “la Caixa” Foundation (LCF/PR/HR23/52430012 and LCF/PR/HR22/52420019). This study was also supported by “la Caixa” Foundation (LCF/PR/HR20/00075 to D.S. and M.A.P.). PID2020-118658RB-I00 (MCIN/AEI/10.13039/501100011033), and PROYE20089DELP (Asociación Española Contra el Cáncer, AECC) to MAP. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the MICIU, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (CEX2020-001041-S funded by MICIU/AEI /10.13039/ 501100011033).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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 International40204706Nature Communicationsopen access