Interleukin-17A Promotes Lung Tumor Progression through Neutrophil Attraction to Tumor Sites and Mediating Resistance to PD-1 Blockade.

ABSTRACT:

Introduction

Proinflammatory cytokine interleukin-17A (IL-17A) is overexpressed in a subset of patients with lung cancer. We hypothesized that IL-17A promotes a protumorigenic inflammatory phenotype and inhibits antitumor immune responses.

Methods

We generated bitransgenic mice expressing a conditional IL-17A allele along with conditional Kras^G12D and performed immune phenotyping of mouse lungs, a survival analysis, and treatment studies with antibodies either blocking programmed cell death 1 (PD-1) or IL-6 or depleting neutrophils. To support the preclinical findings, we analyzed human gene expression data sets and immune profiled patient lung tumors.

Results

Tumors in IL-17:Kras^G12D mice grew more rapidly, resulting in a significantly shorter s

SUBMITTER: Akbay EA 

PROVIDER: S-EPMC5532066 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature