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Journal of Cancer Research and Clinical Oncology

Published in:

02-03-2023 | Gastric Cancer | Research

Palmitic acid combined with γ-interferon inhibits gastric cancer progression by modulating tumor-associated macrophages’ polarization via the TLR4 pathway

Authors: Yan-Yan Zhang, Jian Li, Fan Li, Shuai Xue, Qing-Yu Xu, Ya-Qiong Zhang, Li Feng

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2023

Abstract

Background

Tumor-associated macrophages (TAMs) constitute the main infiltrating immune cells in the solid tumor microenvironment. Amounting studies have analyzed the antitumor effect on immune response induced by Toll-like receptor (TLR) agonists, such as lipopolysaccharide (LPS), γ-interferon (γ-IFN), and palmitic Acid (PA). However, their combined treatment for gastric cancer (GC) has not been illuminated.

Methods

We investigated the relevance of macrophage polarization and the effect of PA and γ-IFN in GC in vitro and in vivo. M1 and M2 macrophage-associated markers were measured by real-time quantitative PCR and flow cytometry, and the activation level of the TLR4 signaling pathways was evaluated by western blot analysis. The effect of PA and γ-IFN on the proliferation, migration, and invasion of GC cells (GCCs) was evaluated by Cell-Counting Kit-8, transwell assays, and wound-healing assays. In vivo animal models were used to verify the effect of PA and γ-IFN on tumor progression, and the M1 and M2 macrophage markers, CD8 + T lymphocytes, regulatory T cells (Treg) cells, and the myeloid-derived suppressor cells (MDSCs) in tumor tissues were analyzed by flow cytometry and immunohistochemical (IHC).

Results

The results showed that this combination strategy enhanced M1-like macrophages and diminished M2-like macrophages through the TLR4 signaling pathway in vitro. In addition, the combination strategy impairs the proliferative and migratory activity of GCC in vitro and in vivo. While, the antitumor effect was abolished using the TAK-424 (a specific TLR-4 signaling pathway inhibitor) in vitro.

Conclusions

The combined treatment of PA and γ-IFN inhibited GC progression by modulating macrophages polarization via the TLR4 pathway.

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Title: Palmitic acid combined with γ-interferon inhibits gastric cancer progression by modulating tumor-associated macrophages’ polarization via the TLR4 pathway
Authors: Yan-Yan Zhang
Jian Li
Fan Li
Shuai Xue
Qing-Yu Xu
Ya-Qiong Zhang
Li Feng
Publication date: 02-03-2023
Publisher: Springer Berlin Heidelberg
Keywords: Gastric Cancer
Gastric Cancer
Interferon
Published in: Journal of Cancer Research and Clinical Oncology / Issue 10/2023
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-023-04655-9

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Background

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