Perioperative systemic immunophenotype following irreversible electroporation (IRE) predicts recurrence

Comprehensive understanding of the immunophenotypic response to local therapy will likely be required to improve outcomes for pancreatic ductal adenocarcinoma (PDAC). While the desmoplastic stroma has rendered PDAC resistant to immunotherapies, irreversible electroporation (IRE), a non-thermal method of tumor ablation, can overcome some of this resistance and immune suppression. We studied the systemic immunophenotype of patients following local treatment of PDAC. Stored lymphocytes from peripheral blood collected pre- and post-operatively for patients with PDAC who underwent surgical treatment from 12/2018 until 12/2019 were prepared for mass cytometry and a 30-marker panel identifying 37 immune-cell clusters were analyzed and compared to all clinical parameters. Stored lymphocytes from patient samples were collected pre-operatively postoperatively (Day 1, 3, 5 and 14) and during surveillance (Month 3, 6, 9 and 12). Thirty patients with locally advanced pancreatic cancer (LAPC) who underwent IRE were evaluated prospectively for changes in their immunophenotype. No significant differences in baseline demographics or tumor markers were identified. CA19-9 levels were significantly higher among patients who developed a recurrence (P=0.03). In the early perioperative period, CD4 and CD8 central memory cells were significantly higher among patients who did not recur (P=0.02 and 0.009 respectively). These findings were maintained in the late (>3 month) surveillance period. Early natural killer (NK) cells were significantly higher among those who did not recur (P=0.004) in the early postoperative period. The early immune-cell populations of CD4 and CD8 central memory cells and early NK cells were significantly higher among populations who did not recur following IRE for PDAC during the study period, with maintenance of the CD4 and CD8 central memory populations during later surveillance. Monitoring the early immunophenotype may offer opportunities to augment the immune response following tumor-disruptive IRE for PDAC.