Ever since Director Qi cut himself off from the people, I wondered why such an aspiring young man and anti-drug hero became corrupt? With my little political awareness, I definitely can’t understand this complicated process, but it reminds me of the tumor problem. Cancerous cells have always been considered the culprit of tumors, but after investigation, it was discovered that the basic question of whether tumor cells build the tumor microenvironment (TME) or TME promotes tumors has not yet been determined.
If Director Qi was a young cell, he would be considered the healthiest cell, but he developed cancer when he was young, which is thought-provoking. There are several theories about the origin of tumors. The most mainstream is the somatic mutation theory (SMT), which believes that cells accumulate a certain amount of mutations and become cancerous. But there is no experimental evidence that a mutant cell can induce tumors after entering healthy tissue. Although some experiments have proved that overall gene knockout can induce tumors, but at this time the entire tissue is already composed of mutant cells, which cannot prove SMT. Another theory is the so-called Tissue Structure Field Theory (TOFT), which holds that changes in the tissue environment come first, and that gene mutations and tumors are only the result of this change.
The organizational structure field is similar to the TME that is often said now. I think it is very similar. Tumor is not a bunch of lone serial killers, but a well-organized underworld. Various cells and signaling factors with different functions in the TME have a complex division of labor (including suppression of immune responses), forming a brand new body tissue. This arena is not always intriguing, killing each other, and the winner takes all. Sometimes they work together, work together, and take advantage of each other. Experiments have shown that only when two types of tumor cells with different properties exist at the same time can they survive together, otherwise they will be destroyed separately. Of course, there are also cells and signaling molecules responsible for communicating with normal tissue substances and energy, and avoiding being attacked by the immune system.
The human body begins with a fertilized egg, and needs to face various environmental stresses such as tissue damage during survival, so normal tissues need complex biological processes to form and maintain, and errors in these processes may form TME. In the 1970s, studies have shown that some tumors can only occur when the tissue is damaged. Now a large number of data show that tumors must be fully prepared for metastasis to other healthy tissues, including immunosuppression. Most tumor cells that leave the primary tissue cannot be transferred to other tissues. Survive. The high degree of functional and genetic heterogeneity of cancer cells within tumor tissue also points to possible environmental errors that cause normal cells to arouse in different ways. So TME is at least as important as mutant cells.
If TME is a real disease then a different strategy is needed for treatment. Traditional chemotherapy only focuses on killing mutated cells, and the results are not satisfactory. Hanzhong’s anti-corruption work has not ended after Director Qi’s death. Although the mechanism of recent checkpoint inhibitors is not very clear, the release of TME immunosuppression is a recognized important factor. Another earlier example is that bisphosphonates inhibit bone metastasis of breast cancer. Although the mechanism is not clear, it may have an important relationship with the regulation of TME because bisphosphonates themselves are not cytotoxic.
If the main components of TME can be found, firstly, imaging technology can be developed to monitor the formation and distribution of TME, or a TME score can be defined, and secondly, these tissues can be safely destroyed with drugs before tumors occur. The development of drugs requires the establishment of new animal and cell models. Currently, the most effective clinical anticancer drug, PD-1 antibody, has little effect on animal models, indicating that it is urgent to improve the preclinical evaluation system. Although chemotherapy and targeted therapy have cured a small number of hematological tumors, solid tumors are still the main killer threatening human health. This point needs to be reflected by the academic community and the pharmaceutical industry. Defining, monitoring, and destroying the TME may be a more effective cancer treatment strategy.
