Assessing Immune Subtype Diversity in Mice

Xavier Vesco

Document Type

Article

Publication Date

8-9-2024

Keywords

JMG

JAX Location

In: Student Reports, Summer 2024, The Jackson Laboratory

Abstract

Immunotherapies are promising cancer treatments that leverage the body’s existing immune system to eliminate cancers. The existing tumor immune microenvironment, critical to immunotherapy response, remains poorly understood due to its complexity. A seminal study by Thorsson et. al, delineated six immune subtypes across 10,000 human tumors spanning 33 cancer types in The Cancer Genome Atlas. These immune subtypes were defined using transcriptomics and characterized by different immune cell proportions, tumor-immune signaling pathways, and patient survival. Such categorization aims to effectively categorize tumor immune states to promote more specific immunology research informed by the common characteristics of many tumors. Our study ascertained if Thorsson’s immune subtypes concept could be extended to mice tumors to create models that reflect the tumor immune state of many human tumors—using a dataset of RNA-sequencing of 2,842 mouse tumors curated from publicly available data, an existing machine-learning tool was employed to predict the immune subtypes defined by Thorsson's study. All six immune subtypes were observed with largely conserved gene signature scores and immune cell type proportions across species. Tumor genetics, tissue of origin, and cancer type emerged as primary determinants for immune subtype classification in mice. The study provides a first step in understanding the heterogeneity of tumor immune microenvironments shared by mouse and human tumors and points to the factors that might be modulated to direct the immune microenvironment toward a desired configuration in mouse models of human cancer.

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