Anlotinib reduces the suppressive capacity of monocytic myeloid-derived suppressor cells and potentiates the immune microenvironment normalization window in a mouse lung cancer model.

ABSTRACT

By exploring the effects of an antiangiogenic small molecule drug named anlotinib on the levels of myeloid-derived suppressor cells (MDSCs) in a mouse xenograft model of lung cancer, the role of anti-angiogenesis in remodeling the immune microenvironment was discussed. In addition, the impact of anlotinib on the normalization of the immune microenvironment and time window was examined, providing a theoretical basis for the optimization of clinical strategies applying anlotinib combined with PD-1 inhibitors. On the basis of the LLC mouse xenograft model, MDSCs and MDSCs + immune microenvironment were examined in tissues, respectively, according to different samples. The former observation included the control (group A) and anlotinib monotherapy (group B) groups; the latter also included the control (group C) and anlotinib monotherapy (group D) groups. The levels of MDSCs in peripheral blood at different time points were analyzed by flow cytometry, and the levels of MDSCs in tissue samples at different time points were evaluated by immunofluorescence and immunohistochemistry. The volumes of subcutaneous xenografts were significantly smaller in the anlotinib treatment group compared with the control group ( P < 0.005). Flow cytometry showed that compared with the control group, the intratumoral percentages of total MDSCs ( P < 0.01) and mononuclear-MDSCs ( P < 0.05) were significantly decreased on days 3 and 17 after anlotinib treatment in peripheral blood samples; however, there was no significant difference in granulocytic-MDSCs changes between the experimental and control groups. Immunofluorescence showed that the levels of MDSCs in both the experimental and control groups reached the lowest points 10 days after drug administration, and were significantly lower in the experimental group than in the control group ( P < 0.05). Anlotinib reduces the levels of MDSCs in the mouse xenograft model of lung cancer, with the characteristics of time window. This study provides a basis for further exploring strategies for anti-angiogenic treatment combined with immunotherapy in lung cancer based on time-window dosing.