Tumor Infiltrating Lymphocytes and Immune-Related Genes as Predictors of Outcome in Pancreatic Adenocarcinoma

Background. We investigated the correlation of pancreatic ductal adenocarcinoma patient prognosis with the presence of tumor infiltrating lymphocytes and expression of 521 immune system genes. Methods. Intratumoral CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. The results were correlated with the gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA). Results. Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37. Discussion. Tumor infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumor infiltrating lymphocyte levels and expression level of the genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors. In this study, we analyzed a total of 12 patients affected by pancreatic tumor split into two different groups based on their outcomes (6 good vs 6 worse prognoses). After the IHC of different populations within cancer, we randomly selected 3 patients for each group and performed a gene expression analysis with Nanostring human PanCancer immune module.