title: A new paradigm for tumor immune escape: β-catenin-driven immune exclusion.
abstract: Increasing evidence is emerging that immunotherapeutic interventions, including checkpoint blockade, are predominantly effective in patients with a pre-existing T cell-inflamed tumor microenvironment. Understanding the mechanisms leading to a non-T cell-inflamed microenvironment are crucial for the development of novel treatment modalities to expand the fraction of patients benefiting from immunotherapy. Based on the hypothesis that one source of inter-patient heterogeneity would lie at differential activation of specific oncogene pathways within the tumor cells themselves, our group recently observed that tumor-cell intrinsic activation of the WNT/β-catenin pathway correlates with absence of T cells from the microenvironment in metastatic melanoma. Genetically-engineered mouse models confirmed a causal relationship, via a mechanism of failed Batf3-lineage dendritic cell recruitment. Hence, tumor cell-intrinsic activation of β-catenin is the first oncogenic pathway demonstrated to exclude the anti-tumor immune response, revealing a potential therapeutic target for improving immunotherapy responsiveness.
authors.affiliation: University of Chicago, 929 E 57th Street, GCIS, Chicago, IL 60637 USA.
authors.forename: Stefani
authors.initials: S
authors.lastname: Spranger
authors.affiliation: University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago, IL 60637 USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
keywords: Checkpoint inhibition; Immune evasion; T-cell infiltration; Tumor microenvironment