Myeloid mechano-metabolic programming restricts anti-tumor immunity-Reference-Cited by-同舟云学术

Myeloid mechano-metabolic programming restricts anti-tumor immunity

Published:2022-09-07 Issue: Volume: Page:
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Author:

Tharp Kevin¹,Kersten Kelly²,Maller Ori¹,Timblin Greg¹,Stashko Connor¹,Hayward Mary-Kate³^ORCID,Berestjuk Ilona¹,Hoeve-Scott Johanna ten⁴,Samad Bushra¹,Combes Alexis¹,Weaver Valerie¹^ORCID,Krummel Matthew¹^ORCID

Affiliation:

1. University of California, San Francisco

2. Netherlands Cancer Institute, Oncode Institute

3. Barts Cancer Institute, Queen Mary University of London

4. University of California, Los Angeles

Abstract

AbstractTumor progression is accompanied by fibrosis, which is associated with diminished anti-tumor immune infiltrate. Here, we demonstrate that tumor infiltrating myeloid cells respond to the stiffened fibrotic tumor microenvironment (TME) by initiating a TGF-beta (TGFβ)-directed, collagen biosynthesis program. A collateral effect of this programming is an untenable metabolic milieu for productive CD8 T cell anti-tumor responses, as collagen-synthesizing macrophages consume environmental arginine, synthesize proline, and secrete ornithine that compromises CD8+T cell function. Thus, a stiff and fibrotic TME may impede anti-tumor immunity not only by direct physical exclusion of CD8+T cells, but also via secondary effects of a myeloid mechano-metabolic programming we identified that creates an inhospitable metabolic milieu for CD8+T cells.

Publisher

Research Square Platform LLC

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