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Open Access Highly Accessed Research article

Transition of tumor-associated macrophages from MHC class IIhi to MHC class IIlow mediates tumor progression in mice

Benfan Wang123, Qinyan Li1, Li Qin1, Siting Zhao1, Jinyan Wang14* and Xiaoping Chen12*

Author Affiliations

1 Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China

2 Department of Medical Biotechnology, School of Life Science, University of Science and Technology of China, Hefei, 230026, China

3 School of Integrated Traditional Chinese & Western Medicine, Anhui University of Traditional Chinese Medicine, Hefei, 230038, China

4 Department of Immunology, Institute of Pathology, College of Basic Medical Science, China Medical University, Shenyang, 110001, China

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BMC Immunology 2011, 12:43  doi:10.1186/1471-2172-12-43

Published: 4 August 2011

Abstract

Background

Tumor-associated macrophages (TAMs) are the most abundant immune cells within the tumor stroma and play a crucial role in tumor development. Although clinical investigations indicate that high levels of macrophage (MΦ) infiltration into tumors are associated with a poor prognosis, the exact role played by TAMs during tumor development remains unclear. The present study aimed to investigate dynamic changes in TAM major histocompatibility complex (MHC) class II expression levels and to assess the effects of these changes on tumor progression.

Results

Significant inhibition of tumor growth in the murine hepatocellular carcinoma Hepa1-6 model was closely associated with partial TAM depletion. Strikingly, two distinct TAM subsets were found to coexist within the tumor microenvironment during Hepa1-6 tumor development. An MHC class IIhi TAM population appeared during the early phase of tumor development and was associated with tumor suppression; however, an MHC class IIlow TAM population became increasingly predominant as the tumor progressed.

Conclusions

Tumor progression was positively correlated with increasing infiltration of the tumor tissues by MHC class IIlow TAMs. Thus, targeting the transition of MΦ may be a novel strategy for drug development and immunotherapy.