Cancer has a profound impact on human life, and immune checkpoint therapy (ICT) has made significant progress in cancer therapy. However, ICT will face various consequences, such as lower overall response rate and immune-related adverse events. To overcome these obstacles, researchers have been exploring novel immune checkpoints. CD300A is a type I transmembrane protein that carries an immunoreceptor tyrosine-based inhibitory motif. It can serve as a potential immune checkpoint and negatively regulate the function of NK cells through its interaction with phosphatidylserine.
Recently, in a research report titled "Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies" published in the international magazine Cancer Biology & Medicine, scientists from the University of Science and Technology of China and other institutions have discovered a new strategy that may enhance the ability of human NK cells to resist hematologic malignancies. By blocking the function of the CD300A protein, the researchers demonstrated that NK cells may significantly enhance their ability to dissolve cancer cells.
In the article, the researchers focused on the CD300A protein, which is a known immune checkpoint present on the surface of NK cells. They found that when CD300A interacts with phosphatidylserine, a special molecule found on the surface of cancer cells, it may inhibit the ability of NK cells to attack and destroy these cells. To address this issue, the researchers developed a novel strategy to block CD300A using a specially designed monoclonal antibody called TX49. By doing so, they were able to enhance the NK cells' cytotoxic capabilities and enable them to more effectively lyse cancer cells in vivo and in vitro.
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The researchers showed that blocking CD300A not only increased the expression of proteins related to cell lysis, but also increased the secretion of cytokines. Cytokines are critical to the coordination of immune responses. This approach significantly improves the survival of mice harboring xenografts of human blood cancer cells and could provide a new treatment option for patients suffering from hematological malignancies and potentially other human cancers. Researcher Dr. Zhigang Tian said that by targeting CD300A, they can potentially enhance the anti-tumor function of NK cells, which may open up new avenues for the treatment of malignant hematological tumors and other cancer types.
Figure 1. Graphic model of the mechanisms underlying blocking CD300A enhances the anti-tumor function of NK cells.
The results of this study indicate that targeting CD300A may serve as a promising complement to immune checkpoint-based cancer immunotherapy. Activating NK cell-based therapies to defend against hematological malignancies may provide some hope for patients with these challenging cancers. In addition, in patients with hematological malignancies or solid tumors, enhanced CD300A expression may be associated with shorter patient survival and a more depleted phenotype of intratumoral NK cells. In summary, the results of this study indicate that CD300A may be used as a potential target to help develop new NK cell-based therapies for the treatment of human hematological malignancies.
Reference
Li, Shuangcheng, et al. "Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies." Cancer Biology & Medicine 21.4 (2024): 331.