Specific antitumour immunity and mechanisms of tumour escape from immunological surveillance

Immune checkpoint inhibitors show promising results in the treatment of patients with malignant neoplasms. However, the objective response to immunotherapy varies depending on the molecular-genetic characteristics of the tumor tissue. While some patients experience a complete and prolonged response, others do not achieve a significant clinical effect even with the presence of microsatellite instability (MSI) or high expression of PD-L1. Consequently, there is a subset of patients who are insensitive to this category of drugs. The formation of specific antitumor immunity, particularly through complementary T-cell receptors to the antigen, plays a critical role. This work considers the mechanisms behind the formation of antitumor immunity, the resistance to therapy with checkpoint inhibitors, and the development of immune cell receptors that are complementary to tumor antigens. Antigenic drift in tumors can destabilize the specifically formed antitumor immunity, leading to disease progression despite immunotherapy. One of the conditions for establishing stable antitumor immunity is the immune system’s ability to continuously synthesize T-cell receptors for various tumor neoantigens. Determining the number of excision circles of recombination TREC and KREC allows for the assessment of the immune system’s capacity to form specific immunity. In oncological patients, a decrease in TREC and KREC levels in the blood can indicate immunodeficiency and may be a marker of the generalization of malignant neoplasms. In the development of specific antitumor immunity, V(D)J DNA recombination contributes to the formation of a diverse repertoire of antigenic receptors in developing T and B cells. Understanding the pathogenesis and clinical picture of antitumor immunity is crucial for effectively controlling the disease and predicting the effectiveness of using checkpoint inhibitors in the immune response.