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Blocking antibody-mediated phosphatidylserine enhances cancer immunotherapy

  • Review – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Cancer immunotherapy is a major breakthrough in tumor therapy and has been used in monotherapy or combination therapy. However, it has been associated with poor immune tolerance in some patients or immune-related adverse events. Therefore, ideal and reliable tumor elimination strategies are urgently needed to overcome these shortcomings. Phosphatidylserine (PS) is a negatively charged phospholipid, usually present in the inner lobules of eukaryotic cell membranes. Under certain physiological or pathological conditions, PS may be exposed on the outer leaflets of apoptotic cells serving as recognition signals by phagocytes and modulating the immune response. On the contrary, increased exposure of PS in the tumor microenvironment can significantly antagonize the body’s anti-tumor immunity, thereby promoting tumor growth and metastasis. During radiotherapy and chemotherapy, PS-mediated immunosuppression increases the PS levels in necrotic tissue in the tumor microenvironment, further suppressing tumor immunity. PS-targeted therapy is a promising strategy in cancer immunotherapy. It inhibits tumor growth and improves the anti-tumor activity of immune checkpoint inhibitors. A comprehensive understanding of the mechanism of PS-targeted therapy opens up a new perspective for future cancer immunotherapies.

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Abbreviations

ADCC:

Antibody-dependent cytotoxicity

Ceacam-1:

Carcinoembryonic Antigen Cell Adhesion Molecule-1

DC:

Dendritic cells

FAS1:

Fascicle protein I

FcRs:

Fc receptors

HMGB1:

High Mobility Group Histone B1

ICIs:

Immune checkpoint inhibitors

IDO:

Indoleamine 2,3-dioxygenase 1

IFN-γ:

Interferon γ

IL-2:

Interleukin 2

1N11:

Monoclonal antibodies

mAbs:

Monoclonal antibodies

MDSCs:

Myeloid-derived suppressor cells

NSCLC:

Non-small cell lung cancer

PS:

Phosphatidylserine

Rac1:

Rac family small GTPase 1

RTKs:

Receptor tyrosine kinases

TAM:

Tyro, Axl, and Mertk

TIM:

T cells, immunoglobulin, and mucin

TME:

Tumor microenvironment

TNF:

Tumor necrosis factor

TIL:

Tumor-infiltrating lymphocytes

VCAM-1:

Vascular cell adhesion molecule 1

β2GP1:

β2 Glycoprotein 1

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Acknowledgements

Thanks to Li Zhang for helping me with the writing process.

Funding

This work was supported by grants from the Training Project of Key Talents of Youth Medicine in Jiangsu province, China (No.QNRC2016330) and High-level talent “six one projects” top talent scientific research project of Jiangsu Province (No.LGY2019034).

Author information

Author notes

  1. Jie Zhang, Zhujiang Dai and Cheng Yan have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China

    Jie Zhang

  2. Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China

    Zhujiang Dai

  3. Dalian Medical University, Dalian, China

    Cheng Yan

  4. Department of General Surgery, Institute of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China

    Daorong Wang & Dong Tang

Authors
  1. Jie Zhang
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  2. Zhujiang Dai
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  3. Cheng Yan
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  4. Daorong Wang
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  5. Dong Tang
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Contributions

JZ and ZD drafted the manuscript in detail. JZ and CY researched the literatures and drew figures. ZD and CY counted and plotted the diagram and table. DT and DW critically revised the article for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Dong Tang.

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Zhang, J., Dai, Z., Yan, C. et al. Blocking antibody-mediated phosphatidylserine enhances cancer immunotherapy. J Cancer Res Clin Oncol 147, 3639–3651 (2021). https://doi.org/10.1007/s00432-021-03792-3

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