N.E. Kushlinskii1, V.V. Maslennikov2, E.A. Korotkova3, V.V. Delektorskaya4, E.S. Gershtein5, N.N. Zybina6, A.A. Alferov7, T.N. Zabotina8, Z.Z. Mamedli9, I.S. Stilidi10

1,3–5,7–10 N.N. Blokhin National Medical Research Center of Oncology
of the Ministry of Health of Russia (Moscow, Russia)

2 «Electrontest» (Moscow, Russia)

6 The Federal State Public Enterprise Nikiforov’s All-Russian Center for Emergency and Radiation Medicine
of the Emergencies Ministry of Russia (the Nikiforov’s NRCERM) (St.-Petersburg, Russia)

The PD-1/PD-L1 system plays an important role in the regulation of antitumor immunity and includes programmed cell death protein 1 (PD-1) receptor and its 2 ligands - PD-L1 and PD-L2. Activation of the PD-1 / PD-L1 pathway stimulates apoptosis of antigen-specific T cells in lymph nodes and simultaneously suppresses apoptosis of regulatory suppressor T cells, which is one of the mechanisms of the tumor’s “escape” from the body’s immune system.

Aim of the study – comparative analysis of sPD-1 and the sPD-L1 levels in blood serum of healthy donors and patients with malignant and benign colon tumors and to assessment of their relationship with clinical and morphological characteristics of the disease.

sPD-1 and sPD-L1 levels were measured in pre-treatment blood serum of 145 patients with colorectal cancer (CRC), 15 patients with benign colon tumors, and 37 healthy control persons. The age of the examined persons ranged from 18 to 85 years. sPD-1 and sPD-L1 concentrations were determined by enzyme immunoassay using Human PD-L1 Platinum ELISA and Human PD-1 ELISA kits (Affimetrix, eBioscience, USA).

Both sPD-L1 and sPD-1 concentrations in the control group were statistically significantly higher than in the general group of patients with colon tumors (medians respectively 13.0 and 8.3 pg/ml – sPD-L1; 55.4 and 37.0 pg/ml – sPD-1; p<0.01 in both cases), but did not depend on benign or malignant character of the tumor. sPD-L1 and sPD-1 concentrations were not associated with histological type and grade of CRC, or with the anatomical localization of the tumor in the affected organ. However, statistically significant decrease of sPD-1/sPD-L1 ratio from 5.6 in patients with G1 tumors to 4.5 in those with G2 and 4.4 – with G3 tumors was observed (p=0.013). Serum sPD-L1 significantly increased with the escalation of the invasion of primary tumor (Т criterion of the TNM system; р=0,022), and was also increased in patients with lymph node or distant metastases. The level of soluble receptor sPD-1 was not associated with the main criteria of CRR progression.

Further studies of sPD-1 and sPD-L1 can improve our understanding of the pathogenesis of CRC, as well as help to assess the possibilities of using the analyzed markers for prognosis and prescription of immunotherapy.

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