Immunomodulatory Effect after Irreversible Electroporation in Patients with Locally Advanced Pancreatic Cancer

Abstract

Purpose. Irreversible electroporation (IRE) has been demonstrated to be a safe and effective method for locally advanced pancreatic cancer (LAPC). The aim of this study was to evaluate the immunomodulatory effect after IRE and to evaluate the prognostic value of variations of the immune parameters in LAPC patients after IRE. Methods. Peripheral blood samples of 34 patients were obtained preoperatively and on the third day (D3) and seventh day (D7) after IRE, respectively. The phenotypes of lymphocytes were analyzed by flow cytometry, and dynamic changes of serum levels of cytokines, complement, and immunoglobulin were assayed by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve and concordance index (C-index) were used to compare the survival predictive ability. Results. There was a transitory decrease followed by a steady increase for CD4+ T cell, CD8+ T cell, NK cell, IL-2, C3, C4, and IgG while a reverse trend was detected for Treg cell, IL-6, and IL10 after IRE. The alteration of CD8+ T cell between D3 and D7 was identified as a prognostic factor for both overall survival (OS) and progression-free survival (PFS). The values of ROC curve (AUC) and C-indexes of the alteration of CD8+ T cell for OS and PFS were 0.816 and 0.773 and 0.816 and 0.639, respectively, which were larger than those of other immune or inflammation-based indexes. Conclusions. This study presented the first evidence of IRE-based immunomodulatory in patients with LAPC. The alteration of CD8+ T cell between D3 and D7 showed relatively good performance and could be used as an effective tool for prognostic evaluation for LAPC patients after IRE.

Irreversible Electroporation: Background, Theory, and Review of Recent Developments in Clinical Oncology

“…137 Further clinical examination has shown that immune modulation occurs quickly after IRE and that attenuation of the highly immunosuppressive environment, as seen by a reduction in regulatory T cells, can be achieved for at least 2 weeks. 138,139 These results are supported by the finding that IRE and anti-PD1 immunotherapy work synergistically to improve survival in a murine model of pancreatic cancer. 140 This study again showed the presence of immune memory that was able to address tumor rechallenge.…”

Dynamics of Cell Death After Conventional IRE and H-FIRE Treatments

“…However, according to the literature, it seems that RCD mechanisms may be preferable over ACD. Studies have shown that both conventional IRE 8,16 and H-FIRE 35 treatments can trigger an anti-tumor immune response. Additionally, our results suggest that H-FIRE can reduce the inflammatory response compared to conventional IRE since the proportion of cells undergoing ACD is lower, but further research would be needed to evaluate this.…”

Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients

“…1 According to the American Joint Committee on Cancer (AJCC) criteria,~40% of PDAC patients (stage III) are diagnosed with locally advanced pancreatic cancer (LAPC), which is defined as the involvement of major vascular structures, leading to unresectable but nonmetastatic diseases. 2,3 For LAPC patients, gemcitabine-based regimens with or without radiation were the standard treatment, the median OS was 9-11 months. 3 FOLFIRINOX chemotherapy has prolonged survival; however, the high rates of the toxicity and adverse events (AEs) of chemotherapy limited the treatment promotion.…”