Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans, ranking sixth in the world in incidence, with about 600,000 new cases and 380,000 deaths every year. At present, the main treatment method for most head and neck cancer is surgical resection supplemented by a comprehensive treatment model of radiotherapy and chemotherapy, but its efficacy is still not ideal, many patients eventually have recurrence or distant metastasis, incurable or metastatic recurrence of patients with low median survival, long-term survival and quality of life of patients are not satisfactory. Therefore, it is imperative to improve the cure rate of head and neck squamous cell carcinoma and optimize the treatment of head and neck squamous cell carcinoma.
Since cancer immunotherapy was named the top ten scientific breakthroughs of the year by Science magazine in 2013, cancer immunotherapy has received a lot of attention. As a promising new therapy, it has gradually been applied to the clinical treatment and basic research of a variety of tumors, including head and neck squamous cell carcinoma, which may bring unexpected curative effects to relapsed or spread advanced head and neck cancer, and undoubtedly provide strong support for anti-cancer treatment. Due to the low toxicity and resistance, high specificity and long-lasting efficacy of immunotherapy, it is gradually becoming the fourth largest treatment for tumors.
Different from chemotherapy, which directly kills tumor cells through cytotoxic action, immunotherapy is the application of various immunological methods to improve the targeted recognition ability of immune effector cells on tumors and immune killing, induce anti-tumor immune response, improve the patient's own immune system, and thus treat tumors. After immune enhancement, the immunity level in the body is at a high and stable activation level, which is conducive to the effector cells to exert the killing effect on the remaining tumor cells after radiotherapy and improve the efficacy.
1. Cytokine therapy
Cytokines are a class of activated immune cells (lymphocytes, monocytes, etc.) and related stromal cells (vascular endothelial cells, fibroblasts, etc.) synthesis and secretion, can regulate immune cell activation and proliferation, with mediated and modulated immune inflammatory response and other biological activities of the substance, belongs to small molecule polypeptides or glycoproteins, at present, the cytokine genes used in tumor biological therapy mainly include interleukin IL-2, interferon IFNα, granulocytes - colony-stimulating factor (GM-CSF) and the like.
The tumor microenvironment of head and neck squamous cell carcinoma is often unbalanced, and there are more immunosuppressive cytokines than immunostimulatory cytokines, thereby promoting the immune escape of head and neck squamous cell carcinoma cells. In the immunotherapy of head and neck squamous cell carcinoma, due to the uncertainty of the effect of single cytokine gene therapy and the toxic side effects of a large number of expressions on the body, people have tried to combine multiple genes or combine cytokine genes with other treatment methods to improve the anti-tumor effect and reduce toxicity.
2. Tumor vaccine treatment
Tumor vaccine therapy is a therapy that uses vaccines to trigger a specific anti-tumor T cell response that destroys tumors. Tumor vaccines mainly include tumor antigen peptide vaccines and synthetic tumor antigen peptides, which are injected into patients alone or together with adjuvants, and the body's specific anti-tumor immune response is stimulated through these tumor antigen peptides.
Tumor vaccine therapy enriches the immunotherapy methods, may have a miracle effect on specific patients, at present, including protein / peptide - dendritic cell vaccine including a variety of tumor vaccine therapy into clinical trial research, through gene sequencing to find the tumor mutation site, how to select the most immunogenic mutation has become a key link in the development of tumor vaccine. At present, tumor vaccines in clinical trials are also used in combination with immune checkpoint inhibitors.
3. Cell adoptive immunotherapy
Cell adoptive immunotherapy is to collect human autoimmune cells, through in vitro activation culture, so that the number of amplification, targeted killing function is enhanced, and then infused back into the patient's body, so as to kill pathogens, cancer cells, mutated cells in the blood and tissues, is currently considered to be the most potential immunotherapy means.
The treatment can adjust the host's immune microenvironment and other states before the cell reinsertion, such as genetic modification of regulatory T cells, so that T cells can recognize and attach specific proteins to tumor cells, thereby improving the anti-tumor effect of the reinfused cells. These cells can be activated in vitro to overcome some inhibitory factors in the body that limit their ability to resist tumors. But the treatment carries the risk of triggering a cytokine storm, a systemic inflammatory response that manifests itself in a large number of pro-inflammatory cytokines with sharply elevated levels.
Iv. Immune checkpoint inhibitor therapy
The body's T cells are very lethal and express certain proteins that have the function of "immune checkpoints" while being activated. The surface of normal cells has corresponding proteins that can be matched to it, which can deactivate the aggression of T cells and play a role in immune escape. Cancer cells also express the same "signal" to trick T cells into dodging attack. Immune checkpoint inhibitor therapy blocks the connection between the surface of the detected cancer cell and its matching protein (CTLA-4 and CD80/CD86, PD-1 versus PD-L1/PD-L2), removing the camouflage mask of the cancer cell. Current inhibitors of programmed cell death 1 receptor (PD-1) have received widespread attention and rapid development, and related inhibitory antibodies have been approved for the treatment of recurrent or metastatic multi-solid tumors. However, the effect of PD-1 inhibitors in the treatment of head and neck cancer still needs to be improved, and better tumor therapy target discovery and a combination of multiple treatment methods are needed to obtain a good prognosis.
As a tumor with high immunodeficiency, the main mechanisms of head and neck squamous cell carcinoma include the introduction of immune tolerance and local immune escape. Studying the pathogenesis, excavating specific antigens, and exploring therapeutic targets will be the key to carrying out immunotherapy, these immunotherapy methods should be based on the specific conditions of patients to synthesize the advantages and disadvantages, organically combine traditional treatment methods, to achieve personalized precision medicine, I believe it will become the main direction of future cancer treatment research.
Although tumor immunotherapy has brought new ideas and hopes for the clinical treatment of head and neck squamous cell carcinoma, it should also be noted that the overall remission rate of immunotherapy still needs to be improved, the treatment plan still needs to be improved, and the antigens in the patient's body are defective in cell function, the tumor immune killing cell effect is transient, and the tumor immune efficacy is low. At present, monoclonal antibodies and CAR-T therapy are hot research and have the potential to become the first-line treatment of head and neck squamous cell carcinoma, but bottlenecks such as how CAR-T cells enter solid tumor cells and the impact of tumor microenvironment need to be solved urgently, and further research is worth looking forward to.
Given the complexity of cancer, the uncertainty and unpredictability of efficacy have always existed, and it has not been possible to accurately determine the disease status and disease classification of advanced cancer to ensure that patients receive the best treatment benefits, and the same is true for immunotherapy. Therefore, immunotherapy is not a panacea, it may enable some patients to survive or even be cured for a long time, but there are still a considerable number of patients who will eventually die. At the same time, receiving immunotherapy also needs to bear a heavy financial burden, so both patients and family members must fully consider their own situation to choose the appropriate treatment method.
For cancer patients with early and low recurrence rates, the choice of immunotherapy needs to be considered comprehensively, and the treatments that can be considered such as non-specific cell immunotherapy and thymus peptides can be considered; for patients with high recurrence rates or advanced stages, specific T cell therapy, immune checkpoint inhibitor therapy, and immune cell (CAR-T/TCR-T therapy) can be considered.
Gentle and safe non-specific immune cells and specific immune cells genetically engineered to be "fast, accurate, stable, and fierce" will reasonably coexist to serve different tumor patient populations. It is believed that adequate molecular typing of patients with head and neck squamous cell carcinoma and careful evaluation of the advantages and disadvantages of immunotherapy and traditional treatment methods, immunotherapy or combination immunotherapy program screening, immunotherapy will bring new hope for improving the prognosis of head and neck cancer patients.
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