Abstract
Immunotherapies have demonstrated limited efficacy in pancreatic ductal adenocarcinoma (PDAC) patients despite their success in treating other tumor types. This limitation is largely due to the relatively immunosuppressive environment surrounding the tumor. A focal ablative technique called irreversible electroporation (IRE) has been shown to modulate this environment, enhancing the efficacy of immunotherapy. One enhancing factor related to improved prognosis is a decrease in regulatory T cells (Treg). This decrease has been previously unpredictable for clinicians using IRE, who currently have limited real-time metrics for determining the activation of the patient’s immune response. Here, we report that larger overall changes in output current are correlated with larger decreases in T cell populations 24 hours post-treatment. This result suggests that clinicians can make real-time decisions regarding optimal follow-up therapy based on the range of output current delivered during treatment. This capability could maximize the immunomodulating effect of IRE in synergy with follow-up immunotherapy. Additionally, these results suggest that feedback from a preliminary IRE treatment of the local tumor may help inform clinicians regarding the timing and choice of subsequent therapies, such as resection, immunotherapy, chemotherapy, or follow-up thermal or non-thermal ablation.
Highlights
Immunotherapies have demonstrated limited efficacy in pancreatic ductal adenocarcinoma (PDAC) patients despite their success in treating other tumor types
This immunosuppressive phenotype of pancreatic cancer derives from specialized immune cells, such as regulatory T (Treg) cells, which mask the tumor to evade the surveillance of immune system[9], resulting in a reduced anti-cancer immune response
Since most types of chemotherapy have been shown to have a cytotoxic effect on immune cells[27], patients demonstrating a decline in Treg cells may benefit from the synergistic effects of irreversible electroporation (IRE) and immunotherapy
Summary
Immunotherapies have demonstrated limited efficacy in pancreatic ductal adenocarcinoma (PDAC) patients despite their success in treating other tumor types. This immunosuppressive phenotype of pancreatic cancer derives from specialized immune cells, such as regulatory T (Treg) cells, which mask the tumor to evade the surveillance of immune system[9], resulting in a reduced anti-cancer immune response Immunotherapy options such as vaccination and checkpoint inhibitors have shown limited success due to the lack of immune cell infiltration to the tumor site and tumor antigen availability[10,11]. The production of oncoantigens along with decreases in suppressive immune cell populations like Treg cells in the ablation zone can lead to increased pro-inflammatory immune response following IRE21 This can potentially facilitate the destruction of both primary and metastatic tumors and prevent the likelihood of cancer recurrence following treatment. This ability to predict changes in the patient’s systemic immune system may improve treatment applications and equips clinicians to maximize post-treatment options
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
