Scientific publications

Inhibition of adjuvant-induced TAM receptors potentiates cancer vaccine immunogenicity and therapeutic efficacy

Feb 28, 2020 | Magazine: Cancer Letters

Diana Llopiz, Marta Ruiz, Leyre Silva, David Repáraz, Belén Aparicio, Josune Egea, Juan J Lasarte, Esther Redin, Alfonso Calvo, Matthew Angel, Jay A Berzofsky, David Stroncek, Pablo Sarobe


Analyzing immunomodulatory elements operating during antitumor vaccination in prostate cancer patients and murine models we identified IL-10-producing DC as a subset with poorer immunogenicity and clinical efficacy. Inhibitory TAM receptors MER and AXL were upregulated on murine IL-10+ DC. Thus, we analyzed conditions inducing these molecules and the potential benefit of their blockade during vaccination. MER and AXL upregulation was more efficiently induced by a vaccine containing Imiquimod than by a poly(I:C)-containing vaccine.

Interestingly, MER expression was found on monocyte-derived DC, and was dependent on IL-10. TAM blockade improved Imiquimod-induced DC activation in vitro and in vivo, resulting in increased vaccine-induced T-cell responses, which were further reinforced by concomitant IL-10 inhibition. In different tumor models, a triple therapy (including vaccination, TAM inhibition and IL-10 blockade) provided the strongest therapeutic effect, associated with enhanced T-cell immunity and enhanced CD8+ T cell tumor infiltration.

Finally, MER levels in DC used for vaccination in cancer patients correlated with IL-10 expression, showing an inverse association with vaccine-induced clinical response. These results suggest that TAM receptors upregulated during vaccination may constitute an additional target in combinatorial therapeutic vaccination strategies.

CITA DEL ARTÍCULO  Cancer Lett. 2021 Feb 28;499:279-289. doi: 10.1016/j.canlet.2020.11.022. 

Our authors

Dr. Diana Llópiz Khatchikian
Dr. Marta Ruiz Egozcue
Research Technician Peptide Research Group
Leyre Silva Vergara
Laboratory technician Vaccine Development Research Group
David Repáraz Pernaut
Belén Aparicio de la Torre
Esther Redín Resano
Dr. Alfonso Calvo González
Researcher | Principal Investigator Solid Tumor Research Program