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Cancer Immunology, Immunotherapy

, Volume 68, Issue 12, pp 1909–1920 | Cite as

Autophagy inhibition induces the repolarisation of tumour-associated macrophages and enhances chemosensitivity of laryngeal cancer cells to cisplatin in mice

  • Ying Guo
  • Yufang Feng
  • Xinhua Cui
  • Qirong Wang
  • Xinliang PanEmail author
Original Article
  • 169 Downloads

Abstract

Tumour-associated macrophages (TAMs) are the key components in the tumour microenvironment. TAMs have two major subtypes, M1 and M2. M1 macrophages are tumour inhibitory, while M2 macrophages are tumour promotive. Repolarising TAMs from M2 to M1 is a promising strategy in cancer treatment. M1 and M2 macrophages were generated from murine bone marrow-derived macrophages (BMDMs). We found that chloroquine (CQ), an autophagy inhibitor, was able to repolarise M2 macrophages to the anti-tumour M1 phenotype. The repolarised macrophages demonstrated higher phagocytotic activity towards Hep-2 laryngeal tumour cells and re-sensitised Hep-2 cells to cisplatin (CDDP) treatment in vitro. While CQ did not demonstrate cytotoxicity to Hep-2 cells in vitro, CQ treatment reduced Hep-2 laryngeal tumour growth in vivo and improved CDDP treatment outcomes. It seems that CQ-induced M2-to-M1 macrophage repolarisation played an important role in tumour growth inhibition, and the CQ/CDDP combined therapy might have clinical potential in laryngeal cancer treatment.

Keywords

Chloroquine (CQ) Tumour-associated macrophages (TAMs) Autophagy inhibition Macrophage repolarisation Hep-2 laryngeal cancer 

Abbreviations

ARG1

Arginase-1

ATCC

American type culture collection

BMDM

Bone marrow-derived macrophage

CDDP

Cisplatin

CM

Conditioned media

CQ

Chloroquine

DMEM

Dulbecco’s modified Eagle medium

FBS

Fetal bovine serum

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

IFN

Interferon

LC3

Microtubule-associated protein 1 light chain 3

IL

Interleukin

LPS

Lipopolysaccharide

M-CSF

Recombinant human macrophage colony stimulating factor

MRC1

Mannose receptor-1

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NOS

Nitric oxide synthase

PBS

Phosphate buffer saline

qRT-PCR

Quantitative real-time polymerase chain reaction

TAM

Tumour-associated macrophage

Notes

Author contributions

YG, YF, XC, QW conducted the experiments, YG and YF analysed the data. YG and XP wrote the manuscript. XP conceived the study.

Funding

This study was funded by the Project of Medical and Health Technology Development Program in Shandong (No. 2017WSB04024).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Animal studies on C57BL/6 mice and nu/nu nude mice complied with the Guidelines for Animal Studies in Shandong University. Ethical Committee in Shandong Provincial Qianfoshan Hospital reviewed and approved this study (#SDQFSH-2017048).

Animal source

C57BL/6 mice and nu/nu nude mice were purchased from Nanjing Model Animal Institute (Nanjing, China).

Cell line authentication

Human laryngeal cancer Hep-2 cell line and GFP-labelled Hep-2-GFP cells were obtained from American Type Culture Collection (ATCC, Manassas, VA, USA) and cells were verified by A Short Tandem Repeat analysis.

Supplementary material

262_2019_2415_MOESM1_ESM.pdf (151 kb)
Supplementary material 1 (PDF 150 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ying Guo
    • 1
  • Yufang Feng
    • 2
  • Xinhua Cui
    • 1
  • Qirong Wang
    • 1
  • Xinliang Pan
    • 3
    Email author
  1. 1.Department of Otorhinolaryngology, Shandong Provincial Qianfoshan HospitalShandong UniversityJinanChina
  2. 2.Department of OtorhinolaryngologyWeifang Yidu Central HospitalWeifangChina
  3. 3.Department of Otorhinolaryngology, Qilu HospitalShandong UniversityJinanChina

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