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

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.