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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 (...

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Autores principales: He, Chaobin, Huang, Xin, Zhang, Yu, Lin, Xiaojun, Li, Shengping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403705/
https://www.ncbi.nlm.nih.gov/pubmed/32508058
http://dx.doi.org/10.1002/ctm2.39
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author He, Chaobin
Huang, Xin
Zhang, Yu
Lin, Xiaojun
Li, Shengping
author_facet He, Chaobin
Huang, Xin
Zhang, Yu
Lin, Xiaojun
Li, Shengping
author_sort He, Chaobin
collection PubMed
description 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.
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spelling pubmed-74037052020-08-06 T‐cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer He, Chaobin Huang, Xin Zhang, Yu Lin, Xiaojun Li, Shengping Clin Transl Med Research Articles 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. John Wiley and Sons Inc. 2020-06-04 /pmc/articles/PMC7403705/ /pubmed/32508058 http://dx.doi.org/10.1002/ctm2.39 Text en © 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
He, Chaobin
Huang, Xin
Zhang, Yu
Lin, Xiaojun
Li, Shengping
T‐cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer
title T‐cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer
title_full T‐cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer
title_fullStr T‐cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer
title_full_unstemmed T‐cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer
title_short T‐cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer
title_sort t‐cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403705/
https://www.ncbi.nlm.nih.gov/pubmed/32508058
http://dx.doi.org/10.1002/ctm2.39
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