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A study of the possible role of Fab-glycosylated IgG in tumor immunity

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Abstract

Previously we reported that administration of IgG could inhibit tumor progression in mouse models. At the same time, we also found that some IgGs have glycosylation modifications on their Fab fragments, which may have different biological functions than non-glycosylated IgG. In this study, we employed mouse tumor models to explore the roles of two different forms of IgG, i.e. Fab-glycosylated and Fab-non-glycosylated IgG, in tumor progression. The two types of IgGs were separated with ConA absorption which could react with glycan on the Fab arm but could not access glycan on the Fc fragment. In addition, we performed cytokine array, ELISA, western blotting, immunocytochemistry and other techniques to investigate the possible mechanisms of the actions of Fab-glycosylated IgG in the models. We found that Fab-glycosylated IgG, unlike Fab-non-glycosylated IgG, did not inhibit tumor growth and metastasis in the model. On the contrary, Fab-glycosylated IgG may bind to antigen-bound IgG molecules and macrophages through the glycosidic chain on the Fab fragment to affect antigen–antibody binding and macrophage polarization, which are likely to help tumor cells to evade the immune surveillance. A new mechanism of immune evasion with Fab-glycosylated IgG playing a significant role was proposed.

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Abbreviations

ConA:

Concanavalin A

DSA:

Datura stramonium agglutinin

ELISA:

Enzyme-linked immunosorbent assay

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

GNA:

Galanthus nivalis agglutinin

HRP:

Horseradish peroxidase

ICAM-1:

Intercellular adhesion molecule 1

IFN-γ:

Interferon gamma

IL:

Interleukin

IVIg:

Intravenous immunoglobulin

LDL R:

Low-density lipoprotein receptor

LPS:

Lipopolysaccharide

MAA:

Maackia amurensis agglutinin

MFI:

Mean fluorescence intensity

MMP 9:

Matrix metallopeptidase 9

MR:

Mannose receptor

SNA:

Sambucus nigra agglutinin

TAM:

Tumor-associated macrophages

P-PE:

P-phycoerythrin

PNA:

Peanut agglutinin

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Acknowledgements

This research was funded by the National Natural Science Foundation of China (81872334) and Li Ka Shing Foundation. The authors would like to thank the Laboratory Animal Center and the Center for Core Facilities of Shantou University Medical College for supporting and providing help to this research.

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Authors and Affiliations

  1. Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, Guangdong, China

    Qian Xu, Xiaodong Deng, Biying Zhang, Chanyuan Zhao, Tao Huang, Yimin Zhang, Zhiming Chen & Jiang Gu

  2. Chongqing Zhifei Biological Products Co., Ltd, Chongqing, 400020, China

    Xiaodong Deng

  3. Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, 515041, Guangdong, China

    Yimin Zhang & Zhiming Chen

  4. Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Jinjiang Hospital for Maternal and Child Health Care, Chengdu, 610066, Sichuan, China

    Jiang Gu

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  1. Qian Xu
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  8. Jiang Gu
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Contributions

JG coordinated the entire project; JG and QX wrote the manuscript; QX, XD, BZ, CZ, TH, YZ, and ZC performed the experiments; QX, BZ, CZ analyzed the data.

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Correspondence to Jiang Gu.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Medical Animal Care and Welfare Committee of Shantou University Medical College (SUMC 2018-128).

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Xu, Q., Deng, X., Zhang, B. et al. A study of the possible role of Fab-glycosylated IgG in tumor immunity. Cancer Immunol Immunother 70, 1841–1851 (2021). https://doi.org/10.1007/s00262-020-02809-z

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  • DOI: https://doi.org/10.1007/s00262-020-02809-z

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