Illustration showing how a protein interferes with tumor infiltration of T cells, which are immune cells./DALL-E
With the rapid development of medical technology, human life expectancy is increasing, but cancer is still considered a difficult disease to cure. Cancer is not only a disease with a high mortality rate, but even if treated, the function of the human body deteriorates rapidly. The World Health Organization (WHO) estimates that the number of cancer deaths worldwide will reach 9.7 million by 2022.
American researchers have discovered a protein that interferes with the activity of T cells that can kill tumor cells. Immunotherapy, which prevents the production of this protein in a cancer patient’s body, can further increase the effectiveness of cancer treatment. By increasing the effectiveness of T cells by blocking protein production, it is expected that it will be possible to treat solid tumors that have had difficulty infiltrating T cells.
The research team led by Lieping Chen, professor at Yale University School of Medicine, published the results of an experiment on mice on the 27th in the international academic journal “Science Immunology”, demonstrating that the “PLA2G10” protein prevents T cells from infiltrating in tumors.
T cells are a type of immune cell, meaning that lymphocytes produced in the bone marrow mature in the thymus. It is the cell most often mentioned in relation to cancer treatment as it plays a role in activating immunity and destroying infected tissue cells. It has recently attracted attention in the field of cancer treatment, such as chimeric antigen receptor T cell (CAR-T) treatment, which has an anti-tumor effect by adding a gene that creates a protein that binds to cancer cells .
However, not all T cells can eliminate tumors in the human body. CAR T-cell therapy, called the dream cancer drug, is used primarily to treat blood cancers that occur in the blood and lymphatic system and does not have a significant effect on solid tumors. According to the research team, half of solid tumors are classified as “cold tumors,” which are unable to infiltrate T cells.
The research team discovered the reason for the inability of T cells to infiltrate the protein “PLA2G10”. As a result of the analysis of genes from cancer patients, the PLA2G10 protein was expressed in unusually high quantities. The research team modified the gene to create experimental mice with PLA2G10 and analyzed how the protein prevents tumor infiltration by T cells compared to normal mice.
The research team analyzed that PLA2G10 does not directly destroy T cells, but prevents tumor infiltration by reducing the mobility of T cells. T cells move in response to the “chemokine”, a protein that causes infected cells. PLA2G10 breaks down phospholipids on the cell surface and produces small metabolites. In particular, it reacts with the cell surface of a chemokine called “CXCL9·10·11′, preventing its correct functioning. If chemokines don’t work properly, T cells can’t move. PLA2G10 acts as a sort of “T cell knockout substance”.
The research team determined that the level of involvement of PLA2G10 varies depending on the organ. In pancreatic cancer, which has a low survival rate, this protein was found to cause a drastic reduction in the quantity and quality of the immune response. Furthermore, the research team announced that through this study, in addition to PLA2G10, factors that can reduce the survival rate of T cells in tumors have been discovered and that they plan to conduct follow-up studies.
The research team explained: “This study revealed that increased PLA2G10 protein is the main cause of T cell suppression” and “it appears that cancer immunotherapy can be strengthened using antibodies that block PLA2G10 protein.” . He then underlined: “It may contribute to the treatment of solid cancer, which has not shown significant efficacy due to insufficient infiltration of T cells.”
References
Scientific Immunology, DOI:
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