T‐cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer

Abstract

Background Irreversible electroporation is shown to induce immune changes in pancreatic cancer while the histology evidences are still lacking. The aim of this study is to show the immune changes in histology and explore whether irreversible electroporation (IRE) can induce immunogenic cell death (ICD) of tumor cells and activate specific immune responses. Methods Subcutaneous and orthotopic pancreatic cancer models were established and used to evaluate the effect of immune modulation of IRE. The infiltration of T cells was assessed in several tissue samples before and after IRE. Abscopal effect was then assessed by comparing the tumor growth of subcutaneous tumors after in situ ablation with IRE or exposure to tumor culture supernatant (TSN) of IRE‐treated Pan02. The expression of damage‐associated molecular patterns (DAMPs) of tumor cells after IRE was detected in vitro. Results IRE could significantly suppress the tumor growth and increase the infiltration of CD8 + T cells. After ablation with IRE or stimulation with TSN of Pan02 treated by IRE, the growth of untreated tumor was suppressed and the effector CD8 + T cells and memory T cells increased significantly in mice. Additionally, the inhibition effect of tumor growth increased along with the increasing strength levels of electroporation. IRE induced ICD of tumor cells by increasing the synthesis and secretion of DAMPs. Conclusions IRE induced local immunomodulation by increasing specific T cells infiltration. Through enhancing specific immune memory, IRE not only led a complete tumor regression in suit, but also induced abscopal effect, suppressing the growth of the latent lesions.

The role of irreversible electroporation in promoting M1 macrophage polarization via regulating the HMGB1-RAGE-MAPK axis in pancreatic cancer

“…Several existing studies indicated that IRE induces immune responses that provide local or systemic protection against tumor recurrence. 18,23,31 This effect has been accompanied by an increase in CD4 + and CD8 + T cells, not only in TME but also in peripheral blood, which could be regarded as T cell activation. 22,23 The activation of the function or increase in the number of T cells can be partly dependent on the increase of co-stimulatory signals, indicating the activation of prime immune responses.…”

“…The electroporation of percutaneous or orthotopic tumor in vivo and was performed according to the methods reported in our previous study. 18 For the electroporation experiments of cells in vitro, tumor cells were trypsinized, resuspended in phosphate-buffered saline (PBS) at 2 × 10 6 cells mL −1 , and added to an electroporation cuvette (1652088; BTX, Holliston, Massachusetts, 01746, USA) embedded with two aluminum plate electrodes 4 mm apart. The cell suspension was in direct contact with the plate electrodes, and subjected to electroporation at room temperature with the following parameters: voltage: 200-600 V; pulse duration: 100 µs; pulse repetition frequency: 1 Hz; number of repetition pulses: 8, 16, and 24.…”

“…16 It has become clear that antitumor therapy is more successful when it can kill tumor cells directly and simultaneously induce an immunogenic form of cell death. 17,18 Immunogenic cell death (ICD), which is characterized by the regulated secretion of damage-associated molecular patterns (DAMPs), mainly including high mobility group B1 (HMGB1), calreticulin, and heat shock protein (HSP), suggests the activation of an immune response specific for cancer cells.- 19,20 Previous studies have shown that IRE could prime or boost tumor-specific immunity. [21][22][23][24] We hypothesize that the molecules released from the dying cells following IRE contribute to the activation of antigen-presenting cells and induce anti-tumor immune responses.…”

Dendritic Cells: Behind the Scenes of T-Cell Infiltration into the Tumor Microenvironment

“…This process preserves adjacent structures by contributing to DC activation and maturation as well as immune cell infiltration. An increase in T-cell levels after IRE has been reported in several mouse models [ 114 , 115 ]. Recently, the combination of IRE and anti-PD1 treatment has been shown to promote selective tumor infiltration by CD8 + T cells, and to significantly suppress tumor growth and prolong survival of immunocompetent mice bearing pancreatic cancer and melanoma [ 116 ].…”

Electroporation-Based Treatments in Urology

“…IRE succeeded in boosting already existing T cell response and in its induction de novo [ 94 ]. Among lymphocytes, CD8+ and CD4+ T-cells are the main agents in anti-tumor response triggered by IRE [ 98 , 99 ]. Few experiments evaluated the possibility of performing IRE together with immunotherapy.…”