Author:
Surendran Abera,Jamalkhah Monire,Poutou Joanna,Birtch Rayanna,Lawson Christine,Dave Jaahnavi,Crupi Mathieu J. F.,Mayer Justin,Taylor Victoria,Petryk Julia,de Souza Christiano Tanese,Moodie Neil,Billingsley Jacob Lecompte,Austin Bradley,Cormack Nicole,Blamey Natalie,Rezaei Reza,McCloskey Curtis W.,Fekete Emily E. F.,Birdi Harsimrat K.,Neault Serge,Jamieson Taylor R.,Wylie Brenna,Tucker Sarah,Azad Taha,Vanderhyden Barbara,Tai Lee-Hwa,Bell John C.,Ilkow Carolina S.
Abstract
IntroductionAdipocytes in the tumour microenvironment are highly dynamic cells that have an established role in tumour progression, but their impact on anti-cancer therapy resistance is becoming increasingly difficult to overlook.MethodsWe investigated the role of adipose tissue and adipocytes in response to oncolytic virus (OV) therapy in adipose-rich tumours such as breast and ovarian neoplasms.ResultsWe show that secreted products in adipocyte-conditioned medium significantly impairs productive virus infection and OV-driven cell death. This effect was not due to the direct neutralization of virions or inhibition of OV entry into host cells. Instead, further investigation of adipocyte secreted factors demonstrated that adipocyte-mediated OV resistance is primarily a lipid-driven phenomenon. When lipid moieties are depleted from the adipocyte-conditioned medium, cancer cells are re-sensitized to OV-mediated destruction. We further demonstrated that blocking fatty acid uptake by cancer cells, in a combinatorial strategy with virotherapy, has clinical translational potential to overcome adipocyte-mediated OV resistance.DiscussionOur findings indicate that while adipocyte secreted factors can impede OV infection, the impairment of OV treatment efficacy can be overcome by modulating lipid flux in the tumour milieu.
Funder
Canadian Institutes of Health Research
Canadian Cancer Society Research Institute
Cancer Research Society
Subject
Immunology,Immunology and Allergy
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献