Tumor immunotherapy is to purposely remove cancerous cells by activating the immune cells in the body. This treatment method has the advantages of high specificity, long duration of action and low side effects, and has been considered as the ultimate means to cure tumors. Tumor cells are abnormal cells that mainly exhibit gene mutations and overexpression of oncogenes. Recent results in tumor genomics have shown that different tumor categories have different mutation abundance. For example, melanoma has a high mutation abundance, with an average of about 200 active mutations per tumor. These mutations or abnormally expressed proteins are the basis on which immune cells recognize cancer cells. Theoretically, immune cells can readily remove abnormal cells and thus nip the tumor in the bud. Dr. Schreiber’s theory of “tumor immune editing” vividly illustrates a dynamic and complex series of interactions between the mutated cells and the immune system in the body. This dynamic process can be divided into three stages: clearance, homeostasis and escape. The tumors we see are the result of immune escape. Tumor immunotherapy is to overcome the mechanism of tumor immune escape so as to reawaken the immune cells to clear the cancer cells. Tumor immunotherapy regimens can be broadly classified into two categories: non-specific and tumor antigen-specific. Non-specific means include immune test site blockade and non-specific activation of immune cells; while tumor antigen-specific approaches are mainly a variety of tumor vaccines and peripatetic immune cell therapies. Both of these categories have clinically approved drugs and both have good clinical efficacy. Some of the main approaches of immunotherapy are briefly described below. Blockers of immune checkpointsImmune checkpoints are a class of immunosuppressive molecules. Their physiological function is to regulate the intensity and breadth of the immune response, thus avoiding damage and destruction of normal tissues. In contrast, tumor cells often use the properties of immune checkpoints to evade immune cells. Dr. Allison proposed to enhance the anti-tumor activity of immune T cells by inhibiting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). Subsequent clinical trials have shown the success of this idea. The first antibody-targeted immune checkpoint treatment, Ipilimumab, was approved by the US FDA in 2011. Phase III clinical results in metastatic melanoma showed that Ipilimumab extended overall survival by nearly 4 months. This data is not encouraging on the surface, but in multiple clinical trials, it has been observed that 13-50% of patients survive beyond 5 years, and some patients are considered almost cured. This is a landmark breakthrough in the treatment of metastatic melanoma. Another immune checkpoint inhibitor that has received continued attention is an antibody to programmed death protein-1 (PD-1) and its ligand. The current phase I clinical results are very encouraging. Because CTLA-4 and PD-1 act at different stages of immune cell activation, the two drugs can be used in different populations or even in combination. In addition, antibodies to PD-1 appear to have a better safety profile, so inhibition of the PD-1/PD-L1 signaling pathway has the potential for broader applications. Although inhibition of immune checkpoints can lead to immune-related side effects such as dizziness, fever, diarrhea, enteritis and pneumonia, and early on even fatal cases, these side effects are generally manageable. Depending on the mechanism of action of the immune checkpoints, it is easier to find appropriate treatment regimens to target and minimize the various side effects. Dr. Rosenberg has done pioneering work in this area and has achieved excellent results in patients with malignant melanoma. In some of their clinical trials, 20-50% of the patients’ tumors were considered “completely cleared”. This is a remarkable achievement. This approach has also been tested in other epithelial tumors, but with poor results. Another improved method of incorporating target therapy into secondary immune cell therapy has recently yielded some promising results, with Dr. June and colleagues introducing a virus with a specific target gene into T cells, allowing viral production of tumor antigen-specific proteins, such as the CD19 receptor, to appear on the surface of the T cells. These CAR-modified T cells (Chimeric Antigen Receptor modified T cells) can target B-cell lymphoma. A typical CAR-modified T cell contains three parts: an extracellular tumor antigen-specific binding protein, a transmembrane region and an intracellular signaling pathway activation region. Clinical trials have demonstrated that this clever design can completely eliminate cancerous cells in certain patients with terminally ill B-cell lymphoma. Relay immune cell therapy is highly tumor antigen specific, but such therapies face a number of challenges, such as the often very low number of tumor cell specific antigens, the short survival period of T cells introduced into the body, the difficulty in getting activated T cells into the tumor tissue, and the immunosuppressive tumor microenvironment. Tumor vaccines are a therapeutic tool with a long history of success in preventing infectious diseases. Therapeutic tumor vaccines use the principles of traditional vaccines to activate the body’s immune cells to specifically attack cancer cells with specific antigens. Scientists have developed a variety of tumor vaccines, including dendritic cell vaccines, inactivated tumor cell vaccines, DNA vaccines, and various adjuvants, and have conducted numerous basic and clinical trials. However, in general, therapeutic tumor vaccines are ineffective and difficult to reproduce. Some recent studies have shown that some chemotherapy, radiotherapy and targeted therapies can induce anti-tumor immune responses. Such approaches, when optimized, could potentially be developed into “in situ vaccines” that activate the immune system to suppress tumor growth. Tumor-associated macrophages Tumor-associated macrophages tend to be the most abundant class of immune cells in solid tumors. Macrophages are originally an important defense cell in the immune system, but tumor-derived factors and their unique tumor microenvironment shape macrophages into tumor “accomplices”. Tumor-associated macrophages are thought to have multiple phenotypes, with M1 tumor-associated macrophages retaining their physiological function as macrophages and having anti-tumor effects. In contrast, M2 tumor-associated macrophages not only promote tumor angiogenesis and tumor migration, but also suppress the anti-tumor immune response in vivo. Therefore, modulating the functional phenotype of tumor-associated macrophages is an area of interest in tumor immunology research. Researchers have explored various means to convert tumor-associated macrophages from M2 to M1, thereby inhibiting tumor growth. For example, reducing the hypoxic state of the tumor microenvironment and targeting the CSF-1 receptor can both alter the phenotype and function of tumor-associated macrophages to achieve anti-tumor effects. Although current monotherapy has achieved good results in some tumors, the efficiency is still low. It is still a difficult task to cure tumors. First, tumors are highly heterogeneous, and this diversity exists not only between different tumors and different patients, but also within the same tumor. Second, tumors have evolved a variety of mechanisms to evade surveillance by the immune system. Therefore, it is difficult for a single therapy to overcome both tumor heterogeneity and various types of immunosuppressive mechanisms. Therefore, simultaneously targeting key mechanisms of tumor immune evasion will be a major option for treating tumors. For example, simultaneous blockade of CTLA4 and PD-1 can achieve better efficacy. Many various combination therapies are also being extensively validated. In recent years, tumor immunotherapy has achieved impressive clinical results and is currently the most promising means of curing malignant tumors. Therefore, researchers are devoting themselves to the research and translation of tumor immunotherapy with unprecedented enthusiasm. It is believed that tumor immunotherapy will continue to create miracles and bring gospel to tumor patients.