4.6 Review

Blocking antibody-mediated phosphatidylserine enhances cancer immunotherapy

Journal

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 147, Issue 12, Pages 3639-3651

Publisher

SPRINGER
DOI: 10.1007/s00432-021-03792-3

Keywords

Phosphatidylserine; Cancer; Immunotherapy; Tumor microenvironment

Categories

Funding

  1. Training Project of Key Talents of Youth Medicine in Jiangsu province, China [QNRC2016330]
  2. High-level talent six one projects top talent scientific research project of Jiangsu Province

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Phosphatidylserine (PS) targeted therapy plays a crucial role in cancer immunotherapy by inhibiting tumor growth, enhancing immunity, and offering new perspectives for future therapies.
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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