Neoadjuvant Chemoradiotherapy Enhances T Cell Infiltration In Pancreatic Ductal Adenocarcinoma But High Percentage Of Regulatory T Cells Associates With Poor Survival

Background Currently, diagnosis with pancreatic ductal adenocarcinoma (PDAC) renders an almost intrinsically poor patient prognosis. Despite complete surgical resection and intense neoadjuvant and/or adjuvant treatment the great majority of patients will ultimately relapse and die from the disease. Further, PDAC has been characterized as highly immune resistant. It is speculated that radiation, chemotherapy, or chemoradiation cause the release of tumor antigens and inflammatory cytokines eventually leading to increased immunogenicity of PDAC. Methods We used computational quantitative multiplex immune fluorescence (qmIF) (n=31) and the NanoString assay (n=34) to quantitatively analyze the effect of neoadjuvant chemoradiation (CRT) on the tumor immune microenvironment (TIME) of PDAC. Results When comparing non-treated (NT) to neoadjuvant chemoradiation (CRT) tumors, the proportion of tumor within the overall tissue sample was markedly lower in treated tumors (figure 1; Mann Whitney U, U=25, p Conclusions We find that CRT greatly alters the TIME of PDAC, altering distributions of tumor cells within the microenvironment and inducing an overall influx of T cells, including cytotoxic, helper, and Treg T cell subsets. In patients receiving CRT, it appears as though the proportion of T cells infiltrating the tumor that are Tregs is closely associated with patient outcome, with a higher proportion of Treg infiltration correlating with a poor outcome. This data suggests that therapies targeting regulatory T cells should be explored in combination with chemo-radiotherapy in PDAC. Ethics Approval The study was approved by Columbia University’s Ethics Board, approval number AAAQ7337.