Profiling the intratumoral immune landscapes of primary and syngeneic Kras-driven sarcoma mouse models

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>The introduction of immunotherapy has revolutionized cancer treatment and fueled interest in the immune cell composition of preclinical tumor models. Both genetically-engineered mouse models and syngeneic cell transplant approaches use immunocompetent mice to study mechanisms driving immunotherapy response and resistance. Due to their rapid and reproducible nature, there has been an expanded interest in developing new syngeneic tools from established primary tumor models. However, there are few analyses directly comparing the immune profiles of primary models with their derived syngeneic counterparts. Here we report comprehensive immunophenotyping of primary tumors from two well-established sarcoma models and four syngeneic allografts derived from these models. We observed that cell lines derived from the same type of genetically engineered primary tumor form allografts with significantly different levels of immune infiltration and intratumoral immune cell composition. Most notable are the differences in the T cell compartment of the syngeneic models, including CD4+ T cell, CD8+ T cell, and regulatory T cell populations – each of which have well-documented roles in tumor response to immunotherapy. Our findings highlight the importance of thorough characterization of syngeneic models prior to their use in preclinical studies in order to maintain scientific rigor and to increase the translatability of findings from bench to bedside.</jats:p>