The review discusses the basic research findings underlying major approaches of the immunotherapy, such as tumor-specific antigens, the role of the immune status of cancer patients and the impact of the immune suppression caused by the developing tumor. The search sources for the appropriate data included MEDLINE, PubMed, and references from the relevant articles. The keywords for the search process were as following: immune surveillance, immunoediting, tumor-associated antigensTumor-associated antigens, neoantigens, cytotoxic lymphocytes (CTL), tumor infiltrating lymphocytes, natural killer cells, lymphokine-activated killers, dendritic cell-based vaccine, CAR-T cells, CAR-T cell therapy. The papers published in English between 1994 and 2022 were considered for the review. The immune system has dynamic interaction with the emerging tumor cells recognized and eliminated by the immune effectors, while genetically transformed resistant clones escape the immune pressure. The tumor has effective mechanisms to counteract the immune system. The antitumor immunotherapy is aimed at overcoming immunosuppressive tumor effects and immunocompromised status of cancer patients and stimulating immune effectors or inhibiting immune suppressing factors. Most tumors have no specific targets that can be hit by the “arrows of the immune response.” Lack of specific antigens means that, despite producing various immunosuppressive factors, tumors cannot induce the generation of special CTL clones. In addition to a number of different mechanisms of tumor evasion from the immune surveillance, the absence of specific bio-targets makes the challenge of induction of a specific antitumor response and substantial enhancement of immunotherapy efficiency into the category of quasi-tasks. Specific CTL clones aimed at an individual or a set of TAAs cannot effectively reveal and destroy a variety of clones of malignantly transformed cells from different normal tissues. Therefore, to improve antitumor immunotherapy results, it is necessary to determine the “antigen signature” of each tumor, achieve inactivation of immune suppressing factors and restore active antitumor immunity.