| First Author | Sivaram N | Year | 2019 |
| Journal | J Clin Invest | Volume | 129 |
| Issue | 8 | Pages | 3264-3276 |
| PubMed ID | 31112530 | Mgi Jnum | J:337611 |
| Mgi Id | MGI:6369915 | Doi | 10.1172/JCI123540 |
| Citation | Sivaram N, et al. (2019) Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer. J Clin Invest 129(8):3264-3276 |
| abstractText | 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. |
