Tumor-intrinsic PIK3CA represses tumor immunogenicity in a model of pancreatic cancer

The presence of tumor-infiltrating T cells is associated with favorable patient outcomes, yet most pancreatic cancers are immunologically silent and resistant to currently available immunotherapies. Here we show using a syngeneic orthotopic implantation model of pancreatic cancer that Pik3ca regulates tumor immunogenicity. Genetic silencing of Pik3ca in KrasG12D/Trp53R172H-driven pancreatic tumors resulted in infiltration of T cells, complete tumor regression, and 100% survival of immunocompetent host mice. By contrast, Pik3ca-null tumors implanted in T cell–deficient mice progressed and killed all of the animals. Adoptive transfer of tumor antigen–experienced T cells eliminated Pik3ca-null tumors in immunodeficient mice. Loss of PIK3CA or inhibition of its effector AKT increased the expression of MHC class I and CD80 on tumor cells. These changes contributed to the increased susceptibility of Pik3ca-null tumors to T cell surveillance. Our results indicate that tumor cell PIK3CA-AKT signaling limits T cell recognition and clearance of pancreatic cancer cells. Strategies that target this pathway may yield an effective immunotherapy for this cancer.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
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Source: Annual Review of Medicine - Category: General Medicine Authors: Tags: Annu Rev Med Source Type: research
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Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
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Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Prog Mol Biol Transl Sci Source Type: research
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Source: CancerNetwork - Category: Cancer & Oncology Authors: Source Type: news
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Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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