Abstract I02: Targeting Innate immunity in pancreatic carcinoma

Abstract

Abstract Pancreatic carcinoma has proven largely resistant to immunotherapies as strategies directly targeting T cells or their receptors have failed in early clinical trials. Basic research has shown that effector T-cell infiltration and phenotype in pancreatic cancer is controlled by diverse innate immune elements including dendritic cells, macrophages and other myeloid cells, and subsets of innate-like T cells. However, the phenotype of macrophages and myeloid cells infiltrating pancreatic carcinoma is, for the most part, highly suppressive of effective adaptive antitumor immunity. Therefore, rather than directly targeting T cells in isolation, immunotherapeutic strategies addressing toleorogenic innate immune cell populations hold greater promise. New potential avenues for immunotherapy include activating or blockade of select innate immune receptors on tumor-associated macrophages to reprogram their suppressive phenotype, targeting the microbiome to modulate the intratumoral inflammatory environment toward a more favorable phenotype, or deleting select subsets of tolerogenic T cells such as delta1 cells. These type of approaches have the potential to enable efficacy for more traditional immunotherapies that target checkpoint or costimulatory receptors, and these strategies can also potentiate the effects of systemic chemotherapy or radiation therapy. Citation Format: George Miller. Targeting Innate immunity in pancreatic carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I02.