Prediction of the response to the immunotherapy with checkpoint inhibitors in patients with advanced solid tumors

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Klin Onkol 2021; 34(Suppl 2): 107-109.

Background: Despite the widespread use of immunotherapy in the treatment of solid tumors, checkpoint inhibitors are only effective in 20–40% of patients. Therefore, the goal of our project is to predict the response to immunotherapy based on a comprehensive analysis of the tumor, its microenvironment and the patient’s immune status. Material and methods: We have prospectively included 70 patients with advanced or metastatic solid tumors who were treated with anti-programmed cell death receptor (PD-1) / anti- programmed cell death receptor ligand (PDL-1) antibodies, in whom we perform complex molecular characterization of the tumor and immunoprofiling of the patient’s peripheral blood. Tumor tissue is assessed by immunohistochemical staining for different subpopulations of immune cells (CD3+, CD4+, CD8+, CD45RO+, FoxP3+) and markers (PD-L1, Tim-3, granzyme B, indolamine 2,3-dioxygenase 1, interferon gamma and mismatch repair proteins). Furthermore, complex genomic sequencing was performed. In peripheral blood cells, we perform descriptive immunoprofiling of basic immune regulators and effectors and their dynamics during immunotherapy. Results: Here we present a preliminary analysis of a descriptive immunoprofile in 70 patients (34 malignant melanomas, 23 on-small cell lung cancer, 8 renal cell carcinomas, 2 colorectal carcinomas, 1 bladder carcinomas, 1 esophageal carcinomas and 1 testicular tumor); the median age was 67 years, 52 men were included. The response to treatment was as follows: complete response (CR) in 10%, partial response (PR) in 24%, stabilization in 10% and disease progression in 52% (not evaluated in 7%). The median progression-free survival was 7.3 months (95% CI 5.1–12.9) and the median overall survival was 17.6 months (95% CI 11.8–25.4). Descriptive immunoprofiling of immune regulators and peripheral blood effectors and their dynamics were performed in some patients. We observed a significantly higher baseline (pre-treatment) number of T cells (P = 0.008) and the proportion of CD8+ cytotoxic T cells (P = 0.013) in responders (CR + PR). No significant differences were found in CD4+, absolute lymphocyte count and regulatory T cells. Conclusion: The conference will present updated and expanded results of response to treatment in relation to peripheral immunoprofile and immunohistochemistry results.

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