Neoadjuvant chemoradiation alters the immune microenvironment in pancreatic ductal adenocarcinoma
Robyn D. Gartrell, Thomas Enzler, Pan Kim, Benjamin T. Fullerton, Ladan Fazlollahi, Andrew Chen, Hanna E. Minns, Subha Perni, Stuart P. Weisberg, Emanuelle M. Rizk, Samuel Wang, Eun Jeong Oh, Xinzheng V. Guo, Codruța Chiuzan, Gulam A. Manji, Susan E. Bates, John A. Chabot, Beth Schrope, Michael D. Kluger, Jean C. Emond, Raúl Rabadán, Donna L. Färber, Helen Remotti, David P. Horowitz, Yvonne M. Saenger
Abstract
macrophages. IG analysis from micro-dissected tissues indicated overexpression of genes involved in antigen presentation, T cell activation, and inflammation in CRT treated tumors. Among treated patients, a higher ratio of Tregs to total T cells was associated with shorter survival time (p = .0121). Despite comparable levels of infiltrating T cells in CRT PDACs to melanoma, PDACs displayed distinct spatial profiles with less T cell clustering as defined by nearest neighbor analysis (p < .001). These findings demonstrate that, while CRT can achieve high T cell densities in PDAC compared to melanoma, phenotype and spatial organization of T cells may limit benefit of T cell infiltration in this immunotherapy-resistant tumor.