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Cell Rep ; 22(11): 2978-2994, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29539425

RESUMO

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.


Assuntos
Aminopiridinas/uso terapêutico , Benzimidazóis/uso terapêutico , Inibidor de Quinase Dependente de Ciclina p15/uso terapêutico , Inibidor de Quinase Dependente de Ciclina p18/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Aminopiridinas/farmacologia , Benzimidazóis/farmacologia , Inibidor de Quinase Dependente de Ciclina p15/farmacologia , Inibidor de Quinase Dependente de Ciclina p18/farmacologia , Humanos , Microambiente Tumoral
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