Enhancing the ability of natural killer cells to combat hematologic malignancies

A new study reveals a groundbreaking approach to immunotherapy, demonstrating that blocking the interaction between the CD300A receptor and phosphatidylserine (PS) significantly enhances the ability of human natural killer (NK) cells to lyse hematologic malignancies (HMs).

Cancer has a profound impact on human life, and immune checkpoint therapy (ICT) has made remarkable strides in cancer treatment. However, ICT faces challenges such as low overall response rates and the emergence of immune-related adverse events. To overcome these hurdles, researchers are exploring new immune checkpoints. CD300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, emerges as a potential immune checkpoint, negatively regulating NK cell function through its interaction with PS.

In a recent study (DOI:10.20892/j.issn.2095-3941.2023.0341) published in Cancer Biology & Medicine, researchers from the University of Science and Technology of China have discovered a novel strategy to enhance the ability of human natural killer (NK) cells to combat hematologic malignancies. By blocking the CD300A protein, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, the team demonstrated a significant boost in the lytic function of NK cells against cancer cells.

The study centered on the CD300A protein, a known immune checkpoint found on the surface of NK cells. The researchers discovered that when CD300A interacts with phosphatidylserine (PS), a molecule present on the surface of cancer cells, it dampens the NK cells' ability to attack and destroy these cells. To counteract this, the team developed a 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, making them more effective at lysing cancer cells both in vitro and in vivo. The study demonstrated that blocking CD300A not only increased the expression of proteins related to cell lysis but also the secretion of cytokines, which are crucial for immune response coordination. This approach led to a significant improvement in the survival rate of mice with xenografted human blood cancer cells, offering a promising therapeutic avenue for patients suffering from hematologic malignancies and potentially other types of cancer.

By targeting CD300A, we can potentially enhance the anti-tumor function of NK cells. This could open new avenues for treating hematologic malignancies and possibly other cancer types."

 Zhigang Tian, lead researcher in the study

The research suggests that targeting CD300A could be a promising addition to immune checkpoint-based cancer immunotherapy. The ability to invigorate NK cell-based treatments against HMs offers new hope for patients with these challenging cancers. The findings also indicate that enhanced expression of CD300A is associated with shorter survival and a more "exhausted" phenotype of intratumoral NK cells in patients with HMs or solid tumors.