Concomitant type I IFN and M-CSF signaling reprograms monocyte differentiation and drives pro-tumoral arginase production.

ABSTRACT:

Background

Type I IFN-based therapies against solid malignancies have yielded only limited success. How IFN affects tumor-associated macrophage (TAM) compartment to impact the therapeutic outcomes are not well understood.

Methods

The effect of an IFN-inducer poly(I:C) on tumor-infiltrating monocytes and TAMs were analyzed using a transplantable mouse tumor model (LLC). In vitro culture systems were utilized to study the direct actions by poly(I:C)-IFN on differentiating monocytes.

Results

We found that poly(I:C)-induced IFN targets Ly6C⁺ monocytes and impedes their transition into TAMs. Such an effect involves miR-155-mediated suppression of M-CSF receptor expression, contributing to restricting tumor growth. Remarkably, further analyses of gene expression

SUBMITTER: Tong Y 

PROVIDER: S-EPMC6354658 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature