Authors: Junke Wang, Jessica Gai, Tengyi Zhang, Nan Niu, Hanfei Qi, Dwayne L. Thomas, Keyu Li, Tao Xia, Christina Rodriguez, Rose Parkinson, Jennifer Durham, Thomas McPhaul, Amol K. Narang, Robert A. Anders, Arsen Osipov, Hao Wang, Jin He, Daniel A. Laheru, Joseph M. Herman, Valerie Lee, Elizabeth M. Jaffee, Elizabeth D. Thompson, Qingfeng Zhu, Lei Zheng
Published: 2024-02-07
Source: Full article
Radiotherapy is hypothesized to have an immune-modulating effect on the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) to sensitize it to anti–PD-1 antibody (a–PD-1) treatment. We collected paired pre- and posttreatment specimens from a clinical trial evaluating combination treatment with GVAX vaccine, a–PD-1, and stereotactic body radiation (SBRT) following chemotherapy for locally advanced PDACs (LAPC). With resected PDACs following different neoadjuvant therapies as comparisons, effector cells in PDACs were found to skew toward a more exhausted status in LAPCs following chemotherapy. The combination of GVAX/a–PD-1/SBRT drives TME to favor antitumor immune response including increased densities of GZMB