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- Title
Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer.
- Authors
Sivaram, Nithya; McLaughlin, Patrick A.; Han, Han V.; Petrenko, Oleksi; Ya-Ping Jiang; Ballou, Lisa M.; Pham, Kien; Chen Liu; van der Velden, Adrianus W. M.; Lin, Richard Z.; Jiang, Ya-Ping; Liu, Chen; van der Velden, Adrianus Wm
- Abstract
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.
- Subjects
PANCREATIC cancer; GENE silencing; CELLULAR recognition; PANCREATIC tumors; T cells; PANCREATIC intraepithelial neoplasia; T cell receptors
- Publication
Journal of Clinical Investigation, 2019, Vol 129, Issue 8, p3264
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI123540