[Relationship between PD-L1 expression and tumor stem cell marker CD44 as a promising basis for the development of new approaches to cancer targeted therapy]. / Svyaz' mezhdu ekspressiei PD-L1 i markerom opukholevykh stvolovykh kletok CD44 kak perspektivnaya osnova dlya razrabotki novykh podkhodov k targetnoi terapii novoobrazovanii.

Immunotherapy of malignant tumors is a rapidly developing area of oncology. PD-1 is a receptor expressed by activated T-lymphocytes. As a result of its interaction with the ligand (PD-L1 or PD-L2), the activity of T-lymphocytes is inhibited and their apoptosis occurs. Drugs that inhibit the interaction of PD-1 with ligands have an immunostimulatory effect and are effective in the treatment of many types of neoplasms: melanoma, lung cancer, bladder cancer, stomach cancer, various lymphomas, etc. However, response to this treatment is observed only in a narrow cohort of patients. To increase the effectiveness of immunotherapy, combined preparations and nanoparticles are being developed and created to enhance the effect of PD-L1 inhibitors, and containing hyaluronic acid as a ligand for the CD44 protein, which is expressed in many human tumors. However, the issue of co-expression of CD44 and PD-L1 remains poorly understood. This review is devoted to describing the features of co-expression and the mechanisms of interaction between CD44 and PD-L1. Promising directions for the development of new approaches to the immunotherapy of malignant tumors are presented.

Automated Assessment of the Area of Infiltration by CD8+ Cells in Gastric Carcinoma and Areas of Normal Mucosa as a Significant Prognostic Factor.

In 139 patients with verified gastric cancer, the infiltration of the postoperative material with CD8+ cells was analyzed. Automated morphometric analysis of immunostained slides was performed separately in different specimen sites (tumor center, invasive edge, and peritumoral mucosa). The mean area of infiltrating CD8+ cells in the tumor center and in the invasive edge was not predictive, while in the peritumoral mucosa it provided a new negative predictive factor (hazard ratio 2.10; confidence interval 0.87-4.92, Cox regression) reliably associated with the TNM stage (hazard ratio 1.91; confidence interval 0.91-4.61, Cox regression).

[Prognostic significance of PD-L1 expression as a potential predictor of survival in gastric cancer]. / Prognosticheskaya znachimost' ekspressii PD-L1 kak potentsial'nogo prediktora vyzhivaemosti pri rake zheludka.

BACKGROUND: Currently, PD-L1 expression in patients with tumors of various localizations is being actively studied. Studies on the expression of PD-L1 detected by clones SP142 and SP263 in gastric cancer (for the drugs atezolizumab and durvalumab, respectively) are rare in the literature. The prognostic role of PD-L1 expression in patients who were not treated with immune checkpoint inhibitors has also not been investigated. OBJECTIVE: To determine the expression level of PD-L1 (clones SP263 and SP142, Roche Ventana) in gastric cancer specimens and evaluate its effect on overall survival in patients who did not receive adjuvant therapy with immune checkpoint inhibitors. MATERIAL AND METHODS: The study included 131 patients with a verified diagnosis of gastric cancer. The material obtained from 127 patients was stained with antibodies to PD-L1 SP263, and from 126 patients - with antibodies to PD-L1 SP142. A multivariate Cox regression model with Wald's step-by-step exclusion algorithm was used to evaluate predictors of survival. RESULTS: The total five-year survival rate of patients in the PD-L1-negative tumor group was significantly lower than the total five-year survival rate of patients in the PD-L1-positive tumor group, which was 50.0% and 40.0% also for both clones (p=0.027). An increase in the expression of PD-L1 clone SP263, determined by both the CPS and TPS method, reduces the chances of death by 1.35 times (p=0.02) and 1.61 times (p=0.004), respectively. An increase in the expression of PD-L1 clone SP142, determined by the CPS method, reduces the chances of death by 1.54 times (p=0.005). CONCLUSION: The survival rate of patients in the group of PD-L1-positive tumors is significantly higher than in patients in the group of PD-L1-negative tumors. Elevated PD-L1 expression, as assessed by the SP263 and SP142 clones, is an important prognostic marker that predicts a higher chance of overall survival for patients, even though these patients are not receiving immune checkpoint inhibitors adjuvant therapy.