Роль факторов иммуносупрессии в прогнозе эффективности клеточной иммунотерапии у пациентов с солидными опухолями

Abstract

Production of different factors with wide immunosuppressive properties by tumor cells is one of the mechanisms that support tumor growth. We think that immunosuppressive action of tumor cells should be taken into account for cellular antitumor therapy optimization. Aim of the study – to evaluate the effectiveness of cellular immunotherapy factors (ISF) for response prediction in patients receiving tag7/PGRP-S gene modified tumor cells (GMV) or autologous dendritic cells vaccine (DCV) for melanoma (Mel), kidney cancer (RCC) and soft tissue sarcoma (STS). Material and methods. We have treated 204 patients with cellular therapy since 2001 till 2016 (88 – GMV, 1 16 – DCV). ISF (MICA, TGF-β, IL-10 и VEGF) were measured in tumor tissue cultures of 88 patients (71 – Mel, 6 – RCC, 11 – STS). Median age of patients was 51 year. Patient were divided as having insufficient response (IR) or sufficient response (SR) for the analysis purpose. Results. ISF concentration in cultures of patients with IR was higher than in patients with SR (р < 0.05). SR could be predicted correctly in 74.4% using ISF. The most important factor was TGF-β1. In the Cox model TGF-β1 and MICA levels were significant predictors of overall survival for Mel patients (р < 0.05). VEGF was the most important factor for time to progression prognosis. Spirman correlations showed moderate significant correlation between ISF (р < 0.05). Conclusions. ISF concentration in cell cultures obtained from the patients with Mel, RCC or STS is important independent predictive factor for time to progression and overall survival. Our data supports rigid selection criteria based on biological properties of tumor cells for patients receiving cellular therapy for solid tumors