There are many ways to classify tumors, according to benign and malignant degree, they can be divided into stage 1, stage 2, stage 3 and stage 4; according to whether they are metastatic or not, they can be divided into in situ tumors and metastatic tumors; according to the site of occurrence, they can be divided into lung cancer, rectal cancer, liver cancer and so on. With the popularity of immunotherapy, especially the “immune test point inhibitors”, the scientific community has recently come up with a new classification: “hot tumor” and “cold tumor”, if you have not heard of them, you are out. If you haven’t heard of it, you are out. Is the temperature of different tumors still different? The term “hot and cold tumors” sounds a bit like the term “Yang and Yin deficiency” in Chinese medicine at first, but it is a new term in the field of authentic Western cancer research. The term “hot and cold” mainly reflects the number, type and status of immune cells in a tumor. Unlike what people think, a tumor is not a large mass of cancer cells gathered together irregularly, but a complex system with not only cancerous cells but also many symbiotic normal cells, such as vascular cells and immune cells, which interact and influence each other. Immune cells are the common, symbiotic normal cell types with cancer cells. If cancer cells are surrounded by more immune cells that recognize cancer cells, then the tumor is a “hot tumor” and vice versa. The reason why we are concerned about the hot and cold cancer cells is that the highly sought-after “immune test point inhibitors” are very effective against a large number of “hot tumors”, but largely ineffective against “cold tumors”. The reason is that the popular “immune point inhibitors” are very effective against a large number of “hot tumors”, but largely ineffective against “cold tumors. Why are tumors “hot and cold”? The occurrence of tumor must avoid the monitoring of immune cells. In the first case, the immune cells have recognized and surrounded the tumor cells, but the tumor cells have evolved to initiate immunosuppression, preventing the immune cells from killing the cancer cells. If we look at these tumors under a microscope, we will see that the cancer cells are actually surrounded by many “righteous” immune cells, but they fail to function, which is called “hot tumor”. The second situation is that the tumor cells pretend to be normal cells very well and hide very deeply, so the immune cells do not find any abnormality at all, and under the microscope, there are few tumor-specific immune cells in the middle of this kind of tumor. The use of immune testing point inhibitor therapy for patients with “hot tumors” will help the existing tumor-specific immune cells to activate, which can kill and remove cancer cells. For “cold tumors”, immunotherapy is ineffective because immune cells can barely recognize tumor cells, and simply relying on immune point inhibitors to activate the immune system is almost ineffective. This is like the rogue in society there are two kinds, one is well hidden, the outside world looks completely good people, such as Yue Buqun, people usually do not recognize; the other is a local bully, such as Simon Qing, and the government collusion, we all know is bad, but also can not do anything about him, but this time if the central anti-corruption, from outside the transfer of a group of troops over, under a thousand fingers, Simon Qing will have to be finished, and Yue Buqun can continue to pseudo-tumor. And Yue Buqun can still continue to disguise! The cold tumor is like Yue Buqun, and the hot tumor is like Simon Qing, the current immunotherapy can only take care of Simon Qing, but not Yue Buqun for the time being. What do tumor cells look like before they can be recognized by immune cells? Immune cells (only T cells here) are definitely “appearance societies”: they specifically identify and kill cells mainly by the characteristics presented on the surface of the cells. Cancer is an endogenous disease, and cancer cells look very much like normal cells in most respects, and although we know there is something wrong with them, it is not easy for immune cells to identify cancer cells by their appearance. However, immune cells can specifically identify cancer cells if two things are met: 1) if there are mutated genes in the cancer cells that create mutant proteins; 2) if mutant protein fragments are presented to the cell surface. This presentation process is done by the “antigen presenting cells”, which can present the mutant protein fragments of the cancer cells themselves and other cells around them. This immunobiology is a bit complicated, so don’t get too hung up on it, just remember that there are two key steps: 1) the mutant protein has to be present and 2) the mutant protein has to be presented to the cell surface. Unfortunately, the vast majority of cancer mutations do not result in mutant proteins, and the vast majority of mutant proteins are not presented to the cell surface, so immune cell recognition of cancer cells is basically a matter of chance. Recent studies have shown that it takes an average of more than 100 mutations for a cancer cell to develop a surface feature that can be recognized by immune cells. This makes the recognition of cancer cells a matter of probability: the greater the number of mutations in a cancer cell, the greater the chance that it will be recognized by the immune system, and the greater the chance that an immune test site inhibitor will work! From the data available now, hot tumors are almost always tumors with many mutations, such as melanoma, such as kidney cancer, such as hereditary rectal cancer. These cancers respond very well to immune test site inhibitors, such as PD1 inhibitors. Knowing this, you will better understand why Pineapple said last time that immunotherapy works better for lung cancer patients who smoke, because the average cancer cell in lung cancer patients who smoke has more than 200 mutations, and some have more than 1000, so lung cancer patients who smoke have relatively more “hot tumors” and these patients are likely to be one of the biggest beneficiaries of immunotherapy now. These patients are likely to be among the largest beneficiaries of immunotherapy. On the contrary, for childhood cancer or non-smoking lung cancer patients, the number of tumors with mutations is low and many of them are “cold tumors”, so it seems that the effect of current immunotherapy is limited for them and other strategies such as targeted drugs are more suitable. It should be noted that “cold” and “hot” tumors have a predictive effect on the effectiveness of immunotherapy, but “cold” and “hot” tumors do not determine the effectiveness of immunotherapy. “is not the only factor that determines the effectiveness of immunotherapy. For unknown reasons, existing immunotherapies are not useful for 100% of “hot tumors”, and some seemingly “cold” cancers respond to immunotherapy. One of the reasons is that in clinical practice, there is no fixed standard for how to determine “cold” and “hot” tumors, and the common approaches include PD-L1 staining, tumor-infiltrating immune cell analysis, tumor composite immune score, and gene mutation analysis. At present, it seems that no single method can accurately predict the effect of immunotherapy, and it is likely that multiple test results will be needed in the future. Immunotherapy is the hottest topic in cancer research in recent years, and the ultimate goal is to let more patients benefit from such therapies. The ultimate goal is to make more patients benefit from these therapies. 1. how to make more “hot tumors” respond to immunotherapy, 2. how to make a large number of “cold tumors” “hot”, and 3. how to treat tumors that never become “hot”. How to treat tumors that never become “hot”. The most important issue for scientists is the fact that they are all concerned about the problem. Many big name scientists and pharmaceutical companies are involved in this, and it is very worthy of attention and expectation.