Abstract IA04: Impact of tumor-resident DC on antitumor immunity

Clearance of tumors relies heavily on the production and maintenance of poly-functional CD8+ T-cell responses. Studies of antiviral and antitumor responses highlight that loss of T-cell effector functions, a phenomenon termed T-cell dysfunction or exhaustion, is associated with tumor evasion and is characteristic of a failed immune response. While this correlation is widely appreciated and the T cell-intrinsic mechanisms are well understood, our current understanding of the T cell-extrinsic stimuli that determine T-cell dysfunction versus sustained effector function remains rudimentary. Studies highlight that T-cell dysfunction is induced in tissue microenvironments characterized by high antigen density such as the tumor or the tumor-draining lymph node. Recent studies using mouse models and patient samples suggest that tumor-resident dendritic cells (DC) can have extensive impact on effector T-cell recruitment and function. Based on these observations, it is conceivable that local, nonmigratory DC subsets can engage directly with antigen-specific T cells and impact their effector function by supplying stimulatory or inhibitory signals. We have established model systems of cancer recapitulating the optimal, immunotherapy-sensitive, and immunotherapy-resistant phenotypes. Our data suggest that optimal antitumor immune responses are associated with the presence of a novel subset of DC, which we termed interferon-stimulated gene (ISG)-DC. Our data highlight that ISG-DC are a distinct subset of DC, capable of activating CD8+ T cells and providing a distinct set of costimulatory molecules to re-engage T cells. Mechanistic studies highlight that ISG-DC use an unconventional way of antigen presentation and are sensitized by tumor-derived dsRNA. In sum, we have identified a novel DC subset, which should be further explored for therapeutic engagement.

Citation Format: Stefani Spranger. Impact of tumor-resident DC on antitumor immunity [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr IA04.