Connecting the Dots: Therapy-Induced Senescence and a Tumor-Suppressive Immune Microenvironment.

ABSTRACT:

Background

Tumor cell senescence is a common outcome of anticancer therapy. Here we investigated how therapy-induced senescence (TIS) affects tumor-infiltrating leukocytes (TILs) and the efficacy of immunotherapy in melanoma.

Methods

Tumor senescence was induced by AURKA or CDK4/6 inhibitors (AURKAi, CDK4/6i). Transcriptomes of six mouse tumors with differential response to AURKAi were analyzed by RNA sequencing, and TILs were characterized by flow cytometry. Chemokine RNA and protein expression were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Therapeutic response was queried in immunodeficient mice, in mice with CCL5-deficient tumors, and in mice cotreated with CD137 agonist to activate TILs. CCL5 expression in refer

SUBMITTER: Vilgelm AE 

PROVIDER: S-EPMC4849355 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature