Radiofrequency ablation - analysis of antitumor immunostimulatory patterns in locally advanced pancreatic cancer

Radiofrequency is a local ablative method based on thermal coagulation and protein denaturation. It has been widely applied in many unresectable and metastatic solid tumours such as liver, lung, prostate, kidney, bone, breast, adrenal gland and spleen, but its application in pancreatic cancer has been very limited so far. Our group has recently shown the feasibility and safety of radiofrequency ablation (RFA) of locally advanced PDAC, with a 24% complication rate and a 2% mortality rate; however, along with the improvement of the learning curve, complications rate halved and mortality annulled. Although it was not the primary aim of our study, data on survival showed a median OS and a median DSS of 20 and 23 months, respectively, representing a promising result. We sought to analyse immunological parameters after RFA of locally advanced pancreatic cancer. This research is focused on exploring immunologic impact of ablation that would explain its survival benefits. Patients undergoing RFA as first step of treatment were enrolled. Immunological parameters were identified in two categories: cells subsets and cytokines. Ten patients underwent RFA as first-step procedure to treat cytologically proven locally advanced pancreatic cancer. .Our data suggest a systemic reaction to the procedure. This reaction is hypothetically different from normal surgical stress or inflammation because we observed a general trend towards a decrease of immunosuppressive chemokines or cells subset. This evidence is supported by a stability of DN (Double negative) T Lymphocytes and Monocytes, trend towards a decrease of Tregs (T regulators) and pDC (plasmocytoid dendritic cells) that, in cancer, exert an immunosuppressive activity. Chemokine production, towards an important inflammatory reaction (see IL-6), through a negative trend of TGF-β and a positive trend of IFN-γ, shows an important systemic effect and a trend in decreasing immunosuppressive agents. Furthermore TEMRA (termina effector memory), the last stage of CD8+ maturation, shows a trend toward a prolonged immunity activity weeks after the procedure, leading to a possible immunity effect either than a normal inflammatory response.In conclusion, these data represent a first characterization of the immunity response generated by pancreatic RFA.