Abstract SY18-02: The relationship between Batf3-DC and antitumor T-cell responses

Abstract

Abstract Cancer immunotherapy has attracted enormous attention and investment, stimulated by successes of immune checkpoint blockade drugs, such as anti-CTLA4 and anti-PD-1. Despite the potential of immunotherapy to eradicate even metastatic cancer, only a minority of cancer patients respond to checkpoint blockade agents. Clinical and preclinical data provide evidence that the presence of tumor-specific CD8 T cells within the tumor microenvironment (TME) is critical for the response to checkpoint blockade. Another major component of tumor-infiltrating immune systems is the mononuclear phagocytic cell compartment, which provides both pro- and antitumoral properties, depending on its composition. A rare subset of conventional dendritic cells, marked by CD103 and the transcription factor Batf3, is required for the uptake, transport, and presentation of tumor-derived antigens to CD8 T cells in the tumor-draining lymph node. Tumors lacking CD103+ dendritic cells do not mount spontaneous antitumor immune responses and fail to respond to checkpoint blockade therapy. Moreover, we observed that absence of this subset of DC is mediating resistance to adoptive T-cell transfer. Analysis of tumor-residing CD103+ dendritic cells revealed that this small subset of cells provides the predominant source of effector T-cell recruiting chemokines (CXCL9 and 10) and is a critical component of the TME. This observation imposes a more detailed and refined analysis of the contribution of tumor-residing dendritic cells to the local antitumor immune response. Citation Format: Stefani Spranger. The relationship between Batf3-DC and antitumor T-cell responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr SY18-02.