As medical technology develops rapidly, human life expectancy is increasing, but cancer is still considered a disease that is difficult to treat. Not only is cancer a disease with a high mortality rate, but even when treated, human body function rapidly deteriorates. The World Health Organization (WHO) estimates that the number of cancer deaths worldwide will reach 9.7 million by 2022.
American researchers have found a protein that interferes with the activity of T cells that can kill cancer cells. Immunotherapy, which prevents the production of this protein in the body of a cancer patient, 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 cancers that have been difficult for T cells to infiltrate.
The research team led by Lieping Chen, a professor at Yale University School of Medicine, published the results of a mouse experiment in the international academic journal ‘Science Immunology’ on the 27th, showing that the ‘PLA2G10’ protein prevents T cells from infiltrating 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. Recently, it has been attracting attention in the field of tumor treatment, such as the ‘chimeric antigen receptor T (CAR-T) cell’ treatment, which has an anti-cancer 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 anticancer drug, is mainly used to treat blood cancers that occur in the blood and lymphatic system, and does not have a significant effect on solid cancers. According to the research team, half of solid tumors are classified as ‘cold tumors’, which are unable to infiltrate T cells.
The research team found the reason for the inability of T cells to infiltrate the protein ‘PLA2G10’. As a result of analyzing the genes of cancer patients, the PLA2G10 protein was unusually expressed in high amounts. 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 ‘Chemokine’, a protein that induces 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 it from functioning properly. If chemokines do not function properly, T cells cannot move. PLA2G10 acts as a kind of ‘T cell exclusion 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 be the cause of drastically lowering the quantity and quality of the immune response. In addition, the research team announced that, in addition to PLA2G10, factors that can lower the survival rate of T cells in tumors were discovered through this study and that they plan to conduct follow-up studies.
The research team explained, “This study revealed that the increase in PLA2G10 protein is the main cause of T cell suppression,” and “It appears that cancer immunotherapy can be strengthened by using antibodies that block PLA2G10 protein.” He then emphasized, “It will be able to contribute to the treatment of solid cancer, which has not shown significant efficacy due to insufficient infiltration of T cells.”
References
Science Immunology, DOI: https://doi.org/10.1126/sciimmunol.adh2334
