Resistance to PD1 blockade in the absence of metalloprotease-mediated LAG3 shedding

Mechanisms of resistance to cancer immunotherapy remain poorly understood. Lymphocyte Activation Gene-3 (LAG3) signaling is regulated by A Disintegrin And Metalloprotease-10 (ADAM10) and ADAM17-mediated cell surface shedding. We developed and utilized mutant mice expressing a metalloprotease-resistance version of LAG3 that can be selectively expressed in T cell subsets. We sorted live T cells from tumors of mice bearing MC38 tumors following 3 treatments with either anti-PD1 or IgG control, and performed single-cell RNAseq using 10X 3' v2 reagents. Overall design: Investigation of transcription profiles of T cells from tumors of wild-type or mutant M38 bearing mice folllowing treatment with anti-PD1 or isotype