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ACS Omega

ACS Omega

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Macrophage Distribution Affected by Virus-Encoded Granulocyte Macrophage Colony Stimulating Factor Combined with Lactate Oxidase.

Published:24 June 2022 DOI: 10.1021/acsomega.2c03213 PMID: 35847295
Chia-Chen Hsieh, Ming-Jung Hsieh, Yu-Hsin Wang and Zi-Xian Liao*, 

Abstract

Oncolytic virotherapy was approved as a localized treatment for advanced melanoma by the US Food and Drug Administration (FDA) in 2015. Granulocyte macrophage colony stimulating factor (GM-CSF) encoded by clinical virus-infected tumor cells, acting as a pro-inflammatory cytokine or growth factor, increases tumor antigen presentation, leading to the activation of macrophages and T cells. Notably, tumor-secreted lactate can promote the suppressive functions of M2-polarized tumor-associated macrophages and subsequently promote tumor growth. Furthermore, the consumption of tumor-secreted lactate has been implicated in the beneficial polarization of macrophages. Here, we report that GM-CSF-encoded recombinant adeno-associated virus (AAV2-GM-CSF) infection in B16-F10 mouse melanoma cells combined with lactate oxidase (LOX) leads to the recruitment of M1 macrophages for the inhibition of cancer cell growth. This study suggests that GM-CSF combined with LOX has potential as cancer virotherapy.

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