Durable Responses to Anti-PD1 and Anti-CTLA4 in a Preclinical Model of Melanoma Displaying Key Immunotherapy Response Biomarkers.

ABSTRACT: Immunotherapy has transformed the management of patients with advanced melanoma, with five-year overall survival rates reaching 52% for combination immunotherapies blocking the cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) and programmed cell death-1 (PD1) immune axes. Yet, our understanding of local and systemic determinants of immunotherapy response and resistance is restrained by the paucity of preclinical models, particularly those for anti-PD1 monotherapy. We have therefore generated a novel murine model of melanoma by integrating key immunotherapy response biomarkers into the model development workflow. The resulting YUMM3.3^UVRc34 (BrafV600E; Cdkn2a-/-) model demonstrated high mutation burden and response to interferon (IFN)γ, including induced expression of a

SUBMITTER: Shklovskaya E 

PROVIDER: S-EPMC9564179 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature