Influence of immune targeted therapy on immune system parameters in patients with endometrial cancer

Immune targeted therapy (ITT) including pembrolizumab, an immune checkpoint inhibitor, and lenvatinib, a targeted drug that blocks receptor tyrosine kinases, is one of the main treatment strategies for advanced endometrial cancer (aEC) patients with proficient mismatch repair (pMMR) and microsatellite stable (MSS). Since immunological mechanisms are involved in the implementation of the therapeutic effects of pembrolizumab and lenvatinib, it is likely that the current state of the patients’ immune system affects the efficacy of ITT. The purpose of the study was to investigate changes in peripheral blood immune parameters depending on the response to therapy in aEC patients who received therapy with pembrolizumab and lenvatinib. Material and Methods. The study included 12 patients with stage II–IV (T2–4N0–2M0–1) aEC with pMMR and MSS, who received therapy with combination of pembrolizumab and lenvatinib. All patients were divided into 2 groups: 1) with disease progression within 6 months of starting ITT (n=4), 2) without signs of progression for more than 6 months (n=8). The immune parameters (the number of VEGFR+ monocytes and VEGFR expression on monocytes, the number of PD-1+ cells in peripheral blood and PD-1 expression on them, the lymphocyte subsets) were evaluated by flow cytometry before starting ITT, 2 and 6 months after therapy. The control group consisted of 39 patients with newly diagnosed EC prior to anticancer therapy. Results. ITT resulted in significant changes in the number of VEGFR+ monocytes and VEGFR expression on monocytes, as well as in the number of PD-1+ cells in peripheral blood and PD-1 expression on them, along with alterations in the lymphocyte subsets. Changes in the immune parameters were related to the response to ITT. At the point of outcome (during disease progression or in the case of long-term response to therapy) the difference in the parameters reached the level of statistical significance. In the case of effective ITT, the immune parameters approached the values observed in control group patients with EC being newly diagnosed. Conclusion. Changes in immune system parameters of aEC patients treated with pembrolizumab in combination with lenvatinib were found to be related to response to therapy.

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