Contribution of Fcγ receptor IIB to creating a suppressive tumor microenvironment in a mouse model

Abstract

Various immune cells are recruited in the tumor microenvironment. It is well established that cellular immune responses, such as cytotoxic or suppressive activities, play an important role in regulating tumor growth and metastasis. However, the contribution of humoral immune responses against tumors is poorly understood. Fc receptors constitute critical elements for the up- or downregulation of immune responses through immune complexes. Here, we examined the potential role of the inhibitory Fc receptor, Fcγ receptor IIB (FcγRIIB), in tumor immunity using a mouse model. Our findings indicated that tumor-specific antibodies are induced in tumor-bearing mice and control tumor immunity. FcγRIIB deletion significantly improved both cellular and humoral immunity against tumors and delayed tumor growth. These findings indicated that spontaneous antibodies against tumors create a suppressive tumor microenvironment through FcγRIIB signaling, thus suggesting an attractive therapeutic target for cancer immunotherapy.

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Abbreviations

BMDMs:

Bone marrow-derived macrophages

FcRs:

Fc receptors

FcγRIIB:

Fcγ receptor IIB

gMDSCs:

Granulocytic MDSCs

HT:

Heterozygous

KO:

Knockout

LLC:

Lewis lung carcinoma

mMDSCs:

Monocytic myeloid-derived suppressor cells

OVA:

Ovalbumin

WT:

Wild-type

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Acknowledgements

The authors thank Dr. Toshiyuki Takai for kindly providing FcγRIIB KO mice and a critical review of this manuscript. The authors would like to thank Enago (http://www.enago.jp) for the English language review.

Funding

This work was supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI Grant nos. 25430103 and 16K07106, Japan.

Author information

Affiliations

Authors

Contributions

HS and CI conceived the concept. HS and YK designed the experiments. YK and SU performed the in vitro and in vivo experiments. HS, YK and SU analyzed the data. HS and YK wrote the paper.

Corresponding author

Correspondence to Hidekazu Shirota.

Ethics declarations

Ethical approval

The study was approved by the Institutional Committee for the Use and Care of Laboratory Animals of Tohoku University. Animal research approval number: 2017-171-1. All in vivo experiments were conducted in strict accordance with good animal practice and complied with ethics committee guidelines of Tohoku University.

Conflict of interest

The authors declare that they have no conflicts of interests.

Animal source

C57Bl/6 mice were obtained from Japan SLC (Hamamatsu, Japan). FcγRIIB KO mice were provided by Takai et al. (Department of Experimental Immunology, Tohoku University, Sendai, Japan).

Cell line authentication

The following cell lines were purchased from American Type Culture collection (Manassas, VA): E.G7, LLC, TC-1 and B16 melanoma. No cell line authentication was necessary.

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Kasahara, Y., Shirota, H., Umegaki, S. et al. Contribution of Fcγ receptor IIB to creating a suppressive tumor microenvironment in a mouse model. Cancer Immunol Immunother 68, 1769–1778 (2019). https://doi.org/10.1007/s00262-019-02413-w

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Keywords

  • Fc receptors
  • Antibody
  • Macrophages
  • Tumor microenvironment
  • Mouse model