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Irreversible electroporation of locally advanced pancreatic cancer transiently alleviates immune suppression and creates a window for antitumor T cell activation
- Source :
- OncoImmunology; November 2019, Vol. 8 Issue: 11
- Publication Year :
- 2019
-
Abstract
- ABSTRACTPurpose: Local tumor ablation through irreversible electroporation (IRE) may offer a novel therapeutic option for locally advanced pancreatic cancer (LAPC). It may also serve as a means of in vivovaccination. To obtain evidence of the induction of systemic antitumor immunity following local IRE-mediated ablation, we performed an explorative immune monitoring study. Methods: In ten patients enrolled in a clinical trial exploring the safety, feasibility, and efficacy of percutaneous image-guided IRE in LAPC, we determined the frequency and activation state of lymphocytic and myeloid subsets in pre- and post-treatment peripheral blood samples using flow cytometry. Tumor-specific systemic T cell responses to the pancreatic cancer associated antigen Wilms Tumor (WT)1 were determined after in vitrostimulation in an interferon-y enzyme-linked immunospot assay (Elispot), at baseline and at 2 weeks and 3 months after IRE. Results: Our data showed a transient decrease in systemic regulatory T cells (Treg) and a simultaneous transient increase in activated PD-1+T cells, consistent with the temporary reduction of tumor-related immune suppression after the IRE procedure. Accordingly, we found post-IRE boosting of a pre-existing WT1 specific T cell response in two out of three patients as well as the de novoinduction of these responses in another two patients. There was a trend for these WT1 T cell responses to be related to longer overall survival (p= .055). Conclusions: These findings are consistent with a systemic and tumor-specific immune stimulatory effect of IRE and support the combination of percutaneous IRE with therapeutic immune modulation.
Details
- Language :
- English
- ISSN :
- 21624011 and 2162402X
- Volume :
- 8
- Issue :
- 11
- Database :
- Supplemental Index
- Journal :
- OncoImmunology
- Publication Type :
- Periodical
- Accession number :
- ejs51002804
- Full Text :
- https://doi.org/10.1080/2162402X.2019.1652532