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J Immunother Cancer. 2015 Sep 15;3:43. doi: 10.1186/s40425-015-0089-6. eCollection 2015.

A new paradigm for tumor immune escape: β-catenin-driven immune exclusion.

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University of Chicago, 929 E 57th Street, GCIS, Chicago, IL 60637 USA.
University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago, IL 60637 USA.


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.


Checkpoint inhibition; Immune evasion; T-cell infiltration; Tumor microenvironment

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