Superantigens are molecules that can stimulate a strong immune response by activating a large number of cytotoxic T cells, which are white blood cells that can eliminate tumor cells. One example of a superantigen is staphylococcal enterotoxin C2 (SEC2), which is produced by a type of bacteria. Scientists have constructed a mutant of SEC2, called ST-4, that can activate cytotoxic T cells more effectively.
However, not all tumor cells are equally susceptible to the attack of cytotoxic T cells. Researchers from the Institute of Applied Ecology, Chinese Academy of Sciences, have discovered that some ovarian cancer cells can resist the effects of SEC2 and ST-4 by changing their stiffness and preventing the destroy made by a protein called perforin in their membranes.
The researchers used transcriptome analysis and atomic force microscopy to study how SEC2 and ST-4 affect two types of ovarian cancer cells: SKOV3 and ES-2. They found that SKOV3 cells were more susceptible to SEC2 and ST-4 than ES-2 cells. The ES-2 cells could escape from SEC2/ST-4-induced cell apoptosis by regulating a signaling pathway involving two proteins: CDC42 and MLC2. In this way, ES-2 cells could avoid the damage caused by perforin, which is released by cytotoxic T cells to destroys cancer cells by creating lesions like pores in their membranes.
The researchers also found that by manipulating the stiffness of ES-2 cells, they could make them more vulnerable to SEC2 and ST-4. This suggests that cell stiffness is an important factor in determining the outcome of superantigen-mediated immune therapy.
This study reveals new insights into how superantigens can be used to fight ovarian cancer and how tumor cells can develop resistance to them. It also suggests potential biomarkers and targets for improving the effectiveness of superantigen drugs.
The study was funded by the Chinese Academy of Sciences and other institutions, and was published in the International Journal of Molecular Sciences under the title “Staphylococcal Enterotoxin C2 Mutant-Induced Antitumor Immune Response Is Controlled by CDC42/MLC2-Mediated Tumor Cell Stiffness”.
Institute of Applied Ecology, Chinese Academy of Sciences