A new paradigm for tumor immune escape: β-catenin-driven immune exclusion. Issue 1 (15th September 2015)

• Record Type: Journal Article
• Authors: Spranger, Stefani; Gajewski, Thomas F.
• Is Part Of: Journal for immunotherapy of cancer. Volume 3:Issue 1(2015)
• Publication Date: 2015-09-15
• Subjects: Tumor microenvironment -- Immune evasion -- Checkpoint inhibition -- T-cell infiltration; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-015-0089-6
• Languages: English
• ISSNs: 2051-1426

Abstract

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.