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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and promoting the transition of M2-TAMs to M1-like macrophages

Authors: Yong Li, Fengjun Cao, Mingxing Li, Pindong Li, Yuandong Yu, Longchao Xiang, Tao Xu, Jinhua Lei, Yun Yan Tai, Jianyong Zhu, Bingbing Yang, Yingpin Jiang, Xiufang Zhang, Long Duo, Ping Chen, Xiongjie Yu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Lysosome-associated agents have been implicated as possible chemo-sensitizers and immune regulators for cancer chemotherapy. We investigated the potential roles and mechanisms of hydroxychloroquine (HCQ) in combination with chemotherapy in lung cancer treatment.

Methods

The effects of combined treatment on non-small cell lung cancer (NSCLC) were investigated using cell viability assays and animal models. The influence of HCQ on lysosomal pH was evaluated by lysosomal sensors and confocal microscopy. The effects of HCQ on the tumour immune microenvironment were analysed by flow cytometry.

Results

HCQ elevates the lysosomal pH of cancer cells to inactivate P-gp while increasing drug release from the lysosome into the nucleus. Furthermore, single HCQ therapy inhibits lung cancer by inducing macrophage-modulated anti-tumour CD8+ T cell immunity. Moreover, HCQ could promote the transition of M2 tumour-associated macrophages (TAMs) into M1-like macrophages, leading to CD8+ T cell infiltration into the tumour microenvironment.

Conclusions

HCQ exerts anti-NSCLC cells effects by reversing the drug sequestration in lysosomes and enhancing the CD8+ T cell immune response. These findings suggest that HCQ could act as a promising chemo-sensitizer and immune regulator for lung cancer chemotherapy in the clinic.
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Metadata
Title
Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and promoting the transition of M2-TAMs to M1-like macrophages
Authors
Yong Li
Fengjun Cao
Mingxing Li
Pindong Li
Yuandong Yu
Longchao Xiang
Tao Xu
Jinhua Lei
Yun Yan Tai
Jianyong Zhu
Bingbing Yang
Yingpin Jiang
Xiufang Zhang
Long Duo
Ping Chen
Xiongjie Yu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0938-5

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