Targeted therapy drug PD-1 inhibitor has now become a star drug, the reason is because many tumors will get rapid therapeutic effect after application, tumor And cancer cells will be killed in large numbers. At present, non-small cell lung cancer and melanoma are widely used. The mechanism of action is mainly to block the way in which tumor cells inhibit immune T cells in the body, thereby enabling T cells to restore the function of inhibiting and killing tumor cells, and finally to remove tumor cells. However, a large number of studies have also found that although the therapeutic effect of PD-1 is very obvious at the beginning of the drug administration, some patients may have cancer or tumors repeated. The cause of tumor recurrence has previously been thought to be related to the heterogeneity of tumor cells, ie, those cells that are sensitive to drug treatment will be killed, but a few genetic mutations, cells that are not sensitive to drugs will continue to survive, with sensitivity The proportion of cells is reduced, and these insensitive cells will gradually increase, which will lead to repeated illnesses. We have previously described the JAK1 and JAK2 gene mutations in the previous article may lead to this situation. However, this is a small probability event after all, and it cannot explain the decline in the effect of so many PD-1 treatments in the later stage. Recently, the research team of Kristen E. Pauken et al. found new reasons for the unsustainable efficacy of PD-1. The relevant research results were published in the famous journal Science (DOI: 10.1126/science.aaf2807). .
It is interesting to note that this study of PD-1 blocker resistance is not a tumor, but an animal model of viral infection. The main reason is that both viral infection and tumor suppressor immune cells are PD-1, and the viral infection model is more controllable. The researchers found that, according to the original idea, when PD-1 is blocked by drugs, the suppressed T cells should gradually return to memory T cells and effector T cells, but after observation, this effect is only transiently produced in the initial stage. However, under long-term observation, the proportion of cells that can stably maintain the above two effectors is very limited. Through various analyses, it was found that the main reason was the role of epigenetics. Although suppressed T cells can be transiently activated by PD-1 blockers, the epigenetic characteristics of these cells remain in a suppressed state, which maintains its original characteristics for a long time. . According to this finding, it can be known that the effect of the immune cells can be transiently increased in the initial stage of treatment of the tumor with the PD-1 inhibitor, resulting in a large amount of elimination of the tumor cells, but if the tumor cells still remain, due to The disappearance of the ergonomic effect, the tumor cells will re-ignite.
Some people may feel pessimistic here. The tumor-targeted therapeutic drug PD-1 inhibitor, which originally brought great hope to everyone, could not get the expected. The effect, then spent all kinds of efforts and spent so much money, not a bubble? Things are always two-sided. We believe that this study will provide a new opportunity to improve the efficacy of PD-1 inhibitor treatment in the future. It can be predicted that the main research directions in the future will be directed to the effects of these PD-1 inhibitors. Mechanisms, if the corresponding drugs are developed and combined with PD-1 inhibitors, I believe that there will be better therapeutic effects, but also need to be completely far from cancer and tumors will not be too far!