O.V. Kovaleva1, V.V. Maslennikov2, N.Yu. Sokolov3, M.M. Kontorshchikov4,  A.S. Mochalova5, N.E. Kushlinskii6

1,3,5,6 N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia)

2 A.I. Evdokimov Moscow University of Medicine and Dentistry  of Ministry of Health of the Russian Federation (Moscow, Russia)

4 Volga Research Medical University (Nizhny Novgorod, Russia)

Colorectal cancer (CRC) is one of the most widespread tumors of the gastrointestinal tract, ranking fourth in morbidity among all malignant neoplasms in the world. Currently, attempts are being made to immunotherapy CRC with drugs that block one of the key immune checkpoints PD-1/PD-L1, taking into account the expression of the programmed cell death receptor PD-1 and its ligand PD-L1 in the tumor. However, despite the success of immunotherapy achieved in the treatment of many other malignant neoplasms, colorectal cancer is extremely difficult to respond to this type of therapy.

Aim of the review – analysis of modern studies devoted to the clinical significance of PD-1 and PD-L1 expression in colon tumors and the peculiarities of the mechanisms of their interaction that prevent the successful therapy of this pathology with checkpoint inhibitors.

The mechanism of action of immunological drugs is aimed at destroying the PD-1 / PD-L1 system, first of all, the most important condition for their use is to determine the appropriate targets in patients: the PD-1 receptor or its ligands PD-L1, PD-L2. This review describes the structure of the function of the PD-1 / PD-L1 system in health and disease. Special attention is paid to the study of the expression of PD-1, PD-L1 in tumors (both directly by tumor and immunocompetent cells infiltrating the primary tumor) and their soluble forms (sPD-1, sPD-L1) in the blood serum of cancer patients. The level of PD-L1 expression in the tumor itself was described as unstable and not very informative as a predictor of survival. At the same time, a high level of PD-L1 expression in its environment significantly correlates with a better prognosis. The first results on the study of sPD-1 and sPD-L1 in patients with CRC are presented. The data on the results of anti-PD-1 / PD-L1 therapy in different types of colon tumors are presented. Described are modern drugs whose action is directed at PD-1 / PD-L1 and the success of their use, both in monotherapy and in combination with other therapeutic agents.

The level of expression of PD-1, PD-L1 in the tumor and soluble forms of these proteins sPD-1 and sPD-L1 in the serum of patients with CRC correlates with some clinical and morphological characteristics of the tumor and can be considered as a potential marker for monitoring the effectiveness of anti-PD-1 / PD-L1 therapy and assessment of patient survival prognosis.

Kovaleva O.V., Maslennikov V.V., Sokolov N.Yu., Kontorshchikov M.M., Mochalova A.S., Kushlinskii N.E. Clinical significance of immune checkpoint PD-1/PD-L1 colorectal cancer. Technologies of Living Systems. 2021. V. 18. № 3. Р. 5−26. DOI: https://doi.org/10.18127/ j20700997-202103-01 (in Russian).

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