With the increasing incidence and mortality of tumors year by year, they have become one of the major threats to human health. Surgery, radiotherapy, chemotherapy and targeted therapy are the main treatments for tumors at present, however, they do not bring long-term survival benefits to patients with advanced tumors. In recent years, the emergence of tumor immunotherapy has brought new hope to tumor patients. Many tumor patients regard it as a “life-saver”, but they do not know that although immunotherapy is “miraculous”, which can reduce pain and prolong survival of tumor patients, not all tumor patients are suitable for its application. What is tumor immunotherapy? Tumor cells are formed by the mutation of normal cells in human body under the influence of environment. Under normal circumstances, the immune system can recognize and remove these tumor cells, but in order to survive and grow, tumor cells can adopt different strategies to make the human immune system suppressed and unable to recognize and kill it normally, so as to survive. Immunotherapy is the process of regaining the ability of immune cells to recognize and destroy tumor cells. It works in two ways: one is to “tell” the immune cells about the characteristics of the tumor cells and let the immune cells locate and kill them. The other is to relieve the tumor cells of their tolerance/shield against immunity, allowing the immune cells to reacquaint themselves with the tumor cells and attack them. PD-1/PD-L1 inhibitors, which are currently very popular, are tumor immunotherapy drugs that can reactivate the damaged immune system to attack tumor cells. In fact, tumor cells are very cunning and will generate various countermeasures against human immunity, putting various “brakes” on various immune cells so that they cannot activate and lose their anti-tumor ability. “By blocking PD-1 antibody, the brakes of T cells will be released and they will regain the ability to kill tumors. II. Who can benefit from immunotherapy? Tumor immunotherapy is considered to be one of the most successful approaches in cancer treatment in recent years. Many tumor patients and their families regard these drugs as “miracle drugs” and “lifesavers”. Many people are blindly optimistic and eager to try these drugs no matter what kind of tumors they have, but in fact, this approach is not scientific. Since PD-1/PD-L1 fight tumors by activating the patient’s own immune system, rather than directly attacking tumor cells, the side effects of PD-1/PD-L1 monoclonal drugs are much less toxic and more effective than chemotherapy drugs. This does sound encouraging. However, it does not mean that immunotherapy is effective for any tumor. Statistically, if PD-1/PD-L1 inhibitors are used alone, their overall effectiveness is generally no more than 20%, and they are very expensive. The anti-tumor efficacy is only substantially improved if the right patients are selected and the class of drugs is used purposefully. Therefore, it is important not to use these drugs blindly or even to “deify” them, but to evaluate them together under the guidance of a medical oncologist before making a decision. Currently, there is no reliable molecular marker that can accurately predict the efficacy of immunotherapy. Recent studies have found that the abundance of tumor cells expressing PD-L1, tumor mutational load (TMB), defective mismatch repair genes (dMMR), and high microsatellite instability (MSI-H) are closely associated with tumor immunotherapy. the higher the expression of PD-L1, the more significant the benefit in immunotherapy, and the lower the expression, the lower the likelihood of benefit. However, it does not mean that higher expression is necessarily effective and lower expression is necessarily ineffective, but only the probability is different. The higher the tumor mutational load, the better the immunotherapy effect, and the tumor mutational load is also a prognostic indicator. Patients with high microsatellite instability have a good immunotherapeutic effect. Clinical observations have also confirmed the efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer, renal cell carcinoma, Hodgkin’s lymphoma, head and neck squamous cell carcinoma, malignant melanoma and solid tumors with high microsatellite instability (MSI-H) or defective mismatch repair genes (dMMR). Studies have also shown that factors such as intestinal flora, smoking status, and long-term antibiotic and hormone use can affect the effectiveness of immunotherapy. In addition, immunotherapy is less effective in patients with EGFR mutations and ALK positivity. III. What are the side effects of immunotherapy? Immunotherapy restores the immune system to kill tumor cells, but also encourages the immune system to attack the normal tissues and organs of the body, which is collectively called immune-related toxic side effects. “This saying also applies to immunotherapy. People focus on the effectiveness of immunotherapy, but ignore the safety issues. It is true that the side effects of immunotherapy are relatively minor, but that does not mean that they are not present, and for some patients, they can be very serious. The side effects of immunotherapy can occur in various parts of the body, including immune-related pneumonia, colitis, hepatitis, pancreatitis, pituitary inflammation, rash, abnormal thyroid function, etc., as well as the highly dangerous lethal myocarditis, acute interstitial pneumonia and acute respiratory distress syndrome. In clinical trials, there have even been people with life-threatening side effects. With the widespread use of immunotherapy, another unexpected side effect began to surface: after a small number of patients received immunotherapy, not only did their tumors not shrink, but they also experienced accelerated progression, with tumors growing more than twice as fast as before treatment. Man is a very complex organism and the toxic side effects of immunotherapy are only just beginning to be understood. This is also a wake-up call for us: immunotherapy can help many people, but it is not a “life-saver” for everyone. Therefore, immunotherapy should not be tried blindly and must be used under the guidance of an experienced medical oncologist. For patients in poor physical condition and those who are older than 65 years old, they should be especially careful and pay close attention to its toxic side effects. 4. 5 reminders of tumor immunotherapy 1. Use should be early. Immunotherapy should be applied as early as possible, do not wait until the patient’s physical condition declines, otherwise the efficacy will be discounted. Some people think that tumor immunotherapy drugs are like nuclear weapons and must be used at the end. If they are used at the beginning, once the tumor becomes drug resistant, there is no other way. Other people think that tumor immunotherapy drugs are the last “killer app”, which can be used only when other drugs are no longer useful. However, a lot of facts prove that these ideas are wrong. More and more experts agree that tumor immunotherapy drugs should not be used only at the end, and patients who have the conditions should use them as early as possible, so that they may be more helpful. 2. There is a “survival trailing effect”. Some patients who use immunotherapy will have high quality long-term survival, such as in melanoma, lung cancer, kidney cancer, etc. Immunotherapy has created a group of “super survivors”. This “trailing effect” can be seen in the fact that after a certain length of immunotherapy, the anti-cancer treatment effect still persists and does not need to be maintained by drugs, which is the biggest difference between immunotherapy and chemotherapy or targeted drugs. 3. Do not follow blindly. Don’t be too superstitious about immunotherapy, although there are breakthroughs, the efficacy is still limited so far. Although PD-1 antibody drugs have created many miracles in tumor treatment, especially in some tumors such as melanoma and renal tumor, the treatment effect is better than traditional chemotherapy, but in fact PD-1 antibody is only effective for some patients, not all patients can benefit from it; and for many tumors, it is only effective for a small number of them. Therefore, we should correctly understand its efficacy and should not be blindly superstitious. 4. Side effects that cannot be ignored. The overall side effects of immunotherapy are very low, but the actual adverse effects are different from those of chemotherapy and targeted therapy. In some effective cases, more severe acute and subacute immune damage to the heart, liver, lungs and intestines can be demonstrated. If not properly treated, it can even cause life-threatening. 5. Pay attention to contraindications. Although tumor immunotherapy is broad-spectrum and the requirements for tumor types are not strict, it is not suitable for everyone. The following 7 types of tumor patients are not suitable for immunotherapy: (1) those with serious autoimmune diseases (2) T-cell lymphoma patients. (2) Patients with T-cell lymphoma, which is itself a lesion of immune cells (3) Uncontrollable infectious diseases (4) Not suitable for organ transplantation for autoimmune system reasons (5) People with organ failure (6) Pregnant or breastfeeding women (7) People who have had more than 4th degree adverse reactions to immunotherapy. Although immunotherapy has great potential and many breakthrough achievements, such as the tumor metastasis in the brain of former U.S. President Jimmy Carter, which disappeared after immunotherapy, this is only an isolated case. At present, the efficacy and suitable population of immunotherapy is still limited, and appropriate efficacy predictors need to be selected for prediction. Nowadays, immunotherapy is still in the clinical exploration stage, and there are still many problems to be solved, but we believe that with the development of medical science and technology, immunotherapy will have a bright future in tumor treatment and become the backbone of the fight against tumor, so let’s wait and see.