Heras-Murillo et al. treated mice with tumor cell lysate-loaded syngeneic splenic selected cDC populations. cDC1-based vaccines induced cancer-specific Teff and Tmem cells, and reduced tumor burden in therapeutic and prophylactic settings more effectively than cDC2-based vaccines, even in hosts lacking cDC1s. cDC1-based treatment in adjuvant and neoadjuvant contexts prevented relapse better than anti-PD-1 therapy. Neoadjuvant cDC1-based therapy boosted tumor-infiltrating CD8+ and CD4+ T resident memory (Trm) cell numbers just prior to tumor remission. Greater CD4+ Trm-like cell abundance correlated with cDC1 presence in human tumors, and patient survival.
Contributed by Paula Hochman
ABSTRACT: 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.
Author Info: (1) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. (2) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Universidad Autnoma d
Author Info: (1) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. (2) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Universidad Autnoma de Madrid, Escuela de Doctorado, Madrid, Spain. (3) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. (4) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. (5) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. (6) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. (7) Program of Immunology and Immunotherapy, CIMA Universidad de Navarra, Pamplona, Spain. (8) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. (9) Program of Immunology and Immunotherapy, CIMA Universidad de Navarra, Pamplona, Spain. Navarra Institute for Health Research (IDISNA), Pamplona, Spain. Centro de Investigacin Biomdica en Red de Cncer (CIBERONC), Madrid, Spain. Nuffield Department of Medicine and Churchill Hospital. University of Oxford, Oxford, UK. (10) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. stefanie.wculek@irbbarcelona.org. Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. stefanie.wculek@irbbarcelona.org. (11) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. dsancho@cnic.es.
