Abstract LB-B02: Orthogonal pathogen challenges in tumor burdened mice reveal systemic impairment of de novo immune responses

Abstract Harnessing immune defense mechanisms has revolutionized cancer therapy. However, the limited efficacy of these approaches across patients and cancer types reflects our incomplete understanding of the factors governing immune responses in cancer. Here, we use orthogonal viral and bacterial challenges in mice with preexisting malignancy to assess functionality of the immune system in cancer. The tumor burdened immune system mounted dampened peripheral T cell responses characterized by reduced proliferation and effector differentiation. Disruptions in T cell activity in vivo were not cell intrinsic but rather due to reduced responses in antigen-presenting cells (APCs). Promoting APC activation was sufficient to restore T cell responses to orthogonal infection. These results demonstrate that tumor development dynamically reshapes the function of the immune macroenvironment, arguing for a deeper understanding of the tumor-experienced systemic context for rational immunotherapeutic design. Citation Format: Kamir Hiam, Breanna Allen, Matthew Spitzer. Orthogonal pathogen challenges in tumor burdened mice reveal systemic impairment of de novo immune responses [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr LB-B02. doi:10.1158/1535-7163.TARG-19-LB-B02