Perioperative systemic immunophenotype following irreversible electroporation (IRE) predicts recurrence

Area of Science:

• Immunology
• Oncology
• Medical Technology

Background:

• Pancreatic ductal adenocarcinoma (PDAC) is often resistant to immunotherapy due to its desmoplastic stroma.
• Irreversible electroporation (IRE), a non-thermal ablation technique, shows potential to overcome immune suppression in PDAC.
• Understanding the systemic immunophenotypic response to local therapies is crucial for improving PDAC outcomes.

Purpose of the Study:

• To investigate the systemic immunophenotypic changes in patients with locally advanced pancreatic cancer (LAPC) following IRE treatment.
• To identify immune cell populations associated with treatment response and recurrence in PDAC patients undergoing IRE.

Main Methods:

• Mass cytometry with a 30-marker panel was used to analyze peripheral blood lymphocytes from PDAC patients.
• Samples were collected pre-operatively and at multiple time points post-operatively and during surveillance (up to 12 months).
• Thirty LAPC patients undergoing IRE were prospectively evaluated for immunophenotypic changes and clinical parameters, including recurrence.

Main Results:

• No significant differences in baseline demographics or tumor markers were observed between groups.
• Patients who developed recurrence had significantly higher CA19-9 levels (P=0.03).
• Higher frequencies of CD4 and CD8 central memory cells (P=0.02, P=0.009) and early natural killer (NK) cells (P=0.004) were observed in patients who did not recur, with sustained CD4/CD8 memory cell levels.

Conclusions:

• Early-phase immune cell populations, specifically CD4/CD8 central memory and NK cells, are significantly higher in patients who do not recur after IRE for PDAC.
• The sustained presence of CD4 and CD8 central memory cells during surveillance suggests their importance in long-term response.
• Monitoring early immunophenotypic changes post-IRE may offer opportunities to enhance the immune response against PDAC.