[HTML][HTML] The CDK4/6 inhibitor abemaciclib induces a T cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade

DA Schaer, RP Beckmann, JA Dempsey, L Huber… - Cell reports, 2018 - cell.com
DA Schaer, RP Beckmann, JA Dempsey, L Huber, A Forest, N Amaladas, Y Li, YC Wang…
Cell reports, 2018cell.com
Abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6), has recently been
approved for the treatment of hormone receptor-positive breast cancer. In this study, we use
murine syngeneic tumor models and in vitro assays to investigate the impact of abemaciclib
on T cells, the tumor immune microenvironment and the ability to combine with anti-PD-L1
blockade. Abemaciclib monotherapy resulted in tumor growth delay that was associated with
an increased T cell inflammatory signature in tumors. Combination with anti-PD-L1 therapy …
Summary
Abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6), has recently been approved for the treatment of hormone receptor-positive breast cancer. In this study, we use murine syngeneic tumor models and in vitro assays to investigate the impact of abemaciclib on T cells, the tumor immune microenvironment and the ability to combine with anti-PD-L1 blockade. Abemaciclib monotherapy resulted in tumor growth delay that was associated with an increased T cell inflammatory signature in tumors. Combination with anti-PD-L1 therapy led to complete tumor regressions and immunological memory, accompanied by enhanced antigen presentation, a T cell inflamed phenotype, and enhanced cell cycle control. In vitro, treatment with abemaciclib resulted in increased activation of human T cells and upregulated expression of antigen presentation genes in MCF-7 breast cancer cells. These data collectively support the clinical investigation of the combination of abemaciclib with agents such as anti-PD-L1 that modulate T cell anti-tumor immunity.
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