Release date: 2015-05-27
The recent rise of immunotherapy has led me to think about whether chemotherapy, the earliest cancer treatment strategy, has helped a lot because of accidentally injuring the immune system. Chemotherapy is an important milestone in cancer treatment, and for the first time, humans have been unable to perform surgery (such as leukemia) tumors for a short time. The basic idea of ​​chemotherapy is to kill all the rapidly dividing cells, which are definitely in this category. But early chemotherapy did not realize that immune cells involved in the removal of tumors are also one of the rapidly dividing cells. Chemotherapy drugs are like killing a part of criminals without indiscriminately killing some of the rapid reaction forces, so the net result is not significant.
If the chemotherapy drugs are only cytotoxic, it seems that these drugs should all suppress the immune system. In fact, one of the most important side effects of chemotherapy drugs is the decline of white blood cells, so many chemotherapy drugs do inhibit the immune system. Many early chemotherapy drugs such as cyclophosphamide and methotrexate are used as immunosuppressive agents for immune diseases. treatment. Killing immune cells directly is only one of the mechanisms that inhibit the immune system, and there are other ways to influence the immune system. For example, the BCR-ABL kinase inhibitor Gleevec (strictly speaking, targeted therapy cannot be regarded as chemotherapy) can selectively inhibit memory T cell differentiation and inhibit the immune system by inhibiting the activation of T cell activation, LCK (also a kinase). Chemotherapy causes a large number of cell deaths to inhibit the immune system and induce immune tolerance, which involves several different pathways. Not only chemotherapy, but also the tumor surgeon often removes the patient's lymph nodes to avoid metastasis, but the lymph nodes are where T cells mature and differentiate, so the anti-cancer effect of the immune system is inevitably reduced. It is also a miracle that this kind of blind person's exploration can actually cure some patients. Of course, the immune system is powerless to some tumors, and it is not harmful.
There are also some chemotherapeutic drugs that activate the immune system through mechanisms that were not realized at the time. For example, DNA-damaging drugs such as topoisomerase inhibitors can trigger a series of biological processes to induce immunogenicity by activating p53. Anthracyclines can increase tumor antigen expression, while low concentrations of cyclophosphamide can selectively inhibit mediator T cells (which themselves suppress the immune system, so lowering such T cells instead activates the immune system). Paclitaxel can directly activate T cells. Although the recently marketed CDK4/6 inhibitor Ibrance only inhibits the cell division process, if the tumor cells are stopped for a long time at a certain stage, the immune system will be noticed and cleaned up. So Ibrance is not only cytostatic but also cytotoxic.
The idea at the beginning of chemotherapy design was relatively simple, and the adverse consequences of the immune system loss against the tumor were not accurately estimated. Now we have made great progress in the function of the immune system in clearing tumor cells. The combination of immunotherapy and chemotherapy based on the different effects of chemotherapy drugs on the immune system is also becoming a new direction of rapid development. Chemotherapy, a relatively old technology, may begin to show real power through collaboration with immunotherapy.
The immune system is just one of many complex factors in biological systems. Receptor desensitization caused by positive and negative feedback mechanisms in biological systems, the activation of alternative functions has greatly reduced the efficacy of many drugs. Many rare side effects are now difficult to predict and explain. These also remind us that although human beings have smartphones and spaceships, the design of new drugs is still in its infancy. But the advancement of technology is also dizzying. I hope that the tumor will soon become an episode in medical history like smallpox.
Source: Internet
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