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Radiofrequency ablation in combination with CD73 inhibitor AB680 reduces tumor growth and enhances anti-tumor immunity in a syngeneic model of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma presents a 5-year overall survival rate of 11%, placing an imperative need for the discovery and application of innovative treatments. Radiofrequency ablation represents a promising therapy for PDA, as studies show it induces coagulative necrosis and a host adaptive...

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Autores principales: Faraoni, Erika Y., Strickland, Lincoln N., O’Brien, Baylee J., Barraza, Joseph F., Thosani, Nirav C., Wray, Curtis J., Mills, Tingting W., Bailey-Lundberg, Jennifer M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9486545/
https://www.ncbi.nlm.nih.gov/pubmed/36147911
http://dx.doi.org/10.3389/fonc.2022.995027
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author Faraoni, Erika Y.
Strickland, Lincoln N.
O’Brien, Baylee J.
Barraza, Joseph F.
Thosani, Nirav C.
Wray, Curtis J.
Mills, Tingting W.
Bailey-Lundberg, Jennifer M.
author_facet Faraoni, Erika Y.
Strickland, Lincoln N.
O’Brien, Baylee J.
Barraza, Joseph F.
Thosani, Nirav C.
Wray, Curtis J.
Mills, Tingting W.
Bailey-Lundberg, Jennifer M.
author_sort Faraoni, Erika Y.
collection PubMed
description Pancreatic ductal adenocarcinoma presents a 5-year overall survival rate of 11%, placing an imperative need for the discovery and application of innovative treatments. Radiofrequency ablation represents a promising therapy for PDA, as studies show it induces coagulative necrosis and a host adaptive immune response. In this work we evaluated the effects of RFA treatment in vivo by establishing a syngeneic mouse model of PDA and performing tumor ablation in one flank. Our studies revealed RFA acutely impaired PDA tumor growth; however, such effects were not sustained one week after treatment. Adenosine (ADO) pathway represents a strong immunosuppressive mechanism that was shown to play a role in PDA progression and preliminary data from ongoing clinical studies suggest ADO pathway inhibition may improve therapeutic outcomes. Thus, to investigate whether ADO generation may be involved in tumor growth relapse after RFA, we evaluated adenosine-monophosphate (AMP), ADO and inosine (INO) levels by HPLC and found they were acutely increased after treatment. Thus, we evaluated an in vivo CD73 inhibition in combination with RFA to study ADO pathway implication in RFA response. Results showed combination therapy of RFA and a CD73 small molecule inhibitor (AB680) in vivo promoted sustained tumor growth impairment up to 10 days after treatment as evidenced by increased necrosis and anti-tumor immunity, suggesting RFA in combination with CD73 inhibitors may improve PDA patient response.
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spelling pubmed-94865452022-09-21 Radiofrequency ablation in combination with CD73 inhibitor AB680 reduces tumor growth and enhances anti-tumor immunity in a syngeneic model of pancreatic ductal adenocarcinoma Faraoni, Erika Y. Strickland, Lincoln N. O’Brien, Baylee J. Barraza, Joseph F. Thosani, Nirav C. Wray, Curtis J. Mills, Tingting W. Bailey-Lundberg, Jennifer M. Front Oncol Oncology Pancreatic ductal adenocarcinoma presents a 5-year overall survival rate of 11%, placing an imperative need for the discovery and application of innovative treatments. Radiofrequency ablation represents a promising therapy for PDA, as studies show it induces coagulative necrosis and a host adaptive immune response. In this work we evaluated the effects of RFA treatment in vivo by establishing a syngeneic mouse model of PDA and performing tumor ablation in one flank. Our studies revealed RFA acutely impaired PDA tumor growth; however, such effects were not sustained one week after treatment. Adenosine (ADO) pathway represents a strong immunosuppressive mechanism that was shown to play a role in PDA progression and preliminary data from ongoing clinical studies suggest ADO pathway inhibition may improve therapeutic outcomes. Thus, to investigate whether ADO generation may be involved in tumor growth relapse after RFA, we evaluated adenosine-monophosphate (AMP), ADO and inosine (INO) levels by HPLC and found they were acutely increased after treatment. Thus, we evaluated an in vivo CD73 inhibition in combination with RFA to study ADO pathway implication in RFA response. Results showed combination therapy of RFA and a CD73 small molecule inhibitor (AB680) in vivo promoted sustained tumor growth impairment up to 10 days after treatment as evidenced by increased necrosis and anti-tumor immunity, suggesting RFA in combination with CD73 inhibitors may improve PDA patient response. Frontiers Media S.A. 2022-09-06 /pmc/articles/PMC9486545/ /pubmed/36147911 http://dx.doi.org/10.3389/fonc.2022.995027 Text en Copyright © 2022 Faraoni, Strickland, O’Brien, Barraza, Thosani, Wray, Mills and Bailey-Lundberg https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Faraoni, Erika Y.
Strickland, Lincoln N.
O’Brien, Baylee J.
Barraza, Joseph F.
Thosani, Nirav C.
Wray, Curtis J.
Mills, Tingting W.
Bailey-Lundberg, Jennifer M.
Radiofrequency ablation in combination with CD73 inhibitor AB680 reduces tumor growth and enhances anti-tumor immunity in a syngeneic model of pancreatic ductal adenocarcinoma
title Radiofrequency ablation in combination with CD73 inhibitor AB680 reduces tumor growth and enhances anti-tumor immunity in a syngeneic model of pancreatic ductal adenocarcinoma
title_full Radiofrequency ablation in combination with CD73 inhibitor AB680 reduces tumor growth and enhances anti-tumor immunity in a syngeneic model of pancreatic ductal adenocarcinoma
title_fullStr Radiofrequency ablation in combination with CD73 inhibitor AB680 reduces tumor growth and enhances anti-tumor immunity in a syngeneic model of pancreatic ductal adenocarcinoma
title_full_unstemmed Radiofrequency ablation in combination with CD73 inhibitor AB680 reduces tumor growth and enhances anti-tumor immunity in a syngeneic model of pancreatic ductal adenocarcinoma
title_short Radiofrequency ablation in combination with CD73 inhibitor AB680 reduces tumor growth and enhances anti-tumor immunity in a syngeneic model of pancreatic ductal adenocarcinoma
title_sort radiofrequency ablation in combination with cd73 inhibitor ab680 reduces tumor growth and enhances anti-tumor immunity in a syngeneic model of pancreatic ductal adenocarcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9486545/
https://www.ncbi.nlm.nih.gov/pubmed/36147911
http://dx.doi.org/10.3389/fonc.2022.995027
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