Abstract B55: Targeting indoleamine 2,3 dioxygenase to improve the efficacy of a therapeutic vaccine against human papillomaviruses-associated tumors

Abstract

The activity of the enzyme indoleamine 2,3 dioxygenase-1 (IDO) has been associated with the maintenance of the immunosuppressive microenvironment in many types of cancers. IDO catalyzes the degradation of tryptophan via the kynurenine pathway, which impacts on the effector activity of immune cells. The role of IDO in immune tolerance observed in human papillomaviruses-associated tumors is poor understood. Here, we targeted IDO to improve the efficacy of a therapeutic protein vaccine against HPV-16-associated tumors. The combination of IDO inhibitors with immunotherapy showed evidence that can support a new antitumor therapeutic approach. In the murine model C57BL/6, different biologic parameters were evaluated in order to determine the activation of the protective immunity obtained by the combined immunotherapy. We observed that isoforms of 1-methyl tryptophan, combined with our therapeutic vaccine, led to an activation of cytotoxic CD8 (+) T cells in mice grafted with tumor cells expressing the HPV-16 oncoproteins. In addition, the combination of melatonin enhanced the efficacy of the immunotherapeutic approach, resulting in the complete eradication of tumor masses. Altogether, our results indicate that blocking the immunosuppressive mechanisms mediated by IDO may improve the antitumor response induced by immunotherapies. Citation Format: Ana Carolina Ramos Moreno, Bruna F. M. M. Porchia, Patrícia da Cruz Souza, Roberta Liberato Pagni, Rafael Pegoraro, Luís Carlos de Souza Ferreira. Targeting indoleamine 2,3 dioxygenase to improve the efficacy of a therapeutic vaccine against human papillomaviruses-associated tumors [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B55.