Journal for ImmunoTherapy of Cancer | |
A new paradigm for tumor immune escape: β-catenin-driven immune exclusion | |
Thomas F. Gajewski1  Stefani Spranger2  | |
[1] University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago 60637, IL, USA;University of Chicago, 929 E 57th Street, GCIS, Chicago 60637, IL, USA | |
关键词: T-cell infiltration; Checkpoint inhibition; Immune evasion; Tumor microenvironment; | |
Others : 1228263 DOI : 10.1186/s40425-015-0089-6 |
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received in 2015-06-19, accepted in 2015-08-25, 发布年份 2015 | |
【 摘 要 】
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.
【 授权许可】
2015 Spranger and Gajewski.
【 预 览 】
Files | Size | Format | View |
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20151013090350301.pdf | 373KB | download |
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