Immune impact of neoadjuvant chemo/radio-therapy in the pancreatic cancer microenvironment. Immune impact of neoadjuvant chemo/radio-therapy in the pancreatic cancer microenvironment

Pancreatic ductal adenocarcinoma (PDAC) has dismal five-year survival (<9%). We examined the impact of neoadjuvant FOLFIRINOX alone or in combination with radiation therapy (conventional radiotherapy, XRT, or stereotactic body radiotherapy, SBRT) on immunologically relevant genes in the PDAC tumor microenvironment (TME). We hypothesize conventional therapies may induce immune alterations in the TME that can be leveraged to enhance the efficacy of immunotherapy in PDAC. PDAC patients who underwent upfront surgical resection or who received neoadjuvant FOLFIRINOX with or without neoadjuvant radiotherapy followed by surgical resection were selected for study. The expression of 730 immunologically relevant transcripts was quantitated using the Nanostring PanCancer immune profiling panel (Platform GPL19965). This analysis identified189 genes that were differentially expressed at the RNA level on the basis of neoadjuvant therapy. On average specimens were obtained 6.6-17.0 weeks after the conclusion of neoadjuvant therapy, depending on treatment group. These data provide insight into the immunological effects of standard of care neoadjuvant therapy for resectable/borderline-resectable PDAC. This work provides data to guide strategic new combination therapies for pancreatic cancer. Overall design: Gene expression profiles were generated on a total of 24 individuals who underwent surgical resection for PDAC at Emory University using the Nanostring PanCancer Immune Profiling Panel (XT-CSO-HIP1-12; Platform GPL19965). Patients who received upfront surgical resection (no neoadjuvant therapy) served as an overall control group for comparison purposes (n=6). Patients who received neoadjuvant FOLFIRINOX served as a secondary comparator-control (n=6). These two groups were compared to each other, and to patients who received neoadjuvant FOLFIRINOX and neoadjuvant radiation therapy (steriotactic body radiotherapy or conventional external beam radiotherapy, n=6 each). Following image acquisition mRNA counts were extracted from raw RCC files using nSolver analysis software v3.0 (Nanostring). Data was then normalized using nSolver.