Antitumor effect on immune control points (PD-1/PD-L1) in malignant neoplasms

Abstract

Introduction. Immunotherapy of malignant neoplasms is a dynamically developing field. Diagnostic possibilities in determining the biomarkers of the tumor response to immunotherapy are discussed. The search for new diagnostic «points» of response is being conducted on the basis of detailed studies of carcinogenesis and cellular biological processes in tumor and unchanged tissues. The aim of this work is to highlight one of the promising points of influence of immunotherapy of malignant tumors of various localizations at the present stage (the PD1/PD-L1 signaling pathway), taking into account the available possibilities of application in practice in the Russian Federation. The analysis of the published activity on immunotherapy with immune checkpoint inhibitors in various malignant tumors was carried out. The search for information research sources was conducted in the open systems E-Library, National Library of Medicine (Pubmed), Cochrane Library for the last 10 years. The article analyzes the progress and prospects in the immunotherapy of malignant tumors of various localizations, including the experience of using the PD-1 inhibitor pembrolizumab in the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine. Information on the use of key diagnostic biomarkers for the prognosis and evaluation of the tumor response to this therapy option is highlighted. The prognostic and diagnostic significance of biomarkers already implemented in practice (PD-L1, MSI) is discussed in the scientific press. Successful immunotherapy has been described in the treatment of uterine body cancer, colon cancer, and colorectal cancer. At the same time, the results of the study of the effectiveness of immunotherapy in uveal melanoma are debatable. Conclusion. The effect on the PD1/PD-L1 signaling pathway with the use of immune checkpoint inhibitors (pembrolizumab, atezolizumab, etc.) is one of the promising directions in the treatment of ZNO of various localizations. The determination of a number of biomarkers by immunohistochemical method, by PCR (PD-L1 receptor, MSI) allows us to identify those cases of ZNO, immunotherapy of which can give a positive effect. New approaches are being sought to influence the signaling pathways of immune control points through the development of new combined drugs. And research is also continuing to determine the predictivity of already used biomarkers of the response to immunotherapy.