Tumor-associated macrophages restrict CD8 + T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment.

Autor: Tharp KM; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA, USA., Kersten K; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA., Maller O; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA, USA., Timblin GA; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA, USA., Stashko C; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA, USA., Canale FP; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland., Menjivar RE; Department of Surgery, University of Michigan, Ann Arbor, MI, USA., Hayward MK; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA, USA., Berestjuk I; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA, USA., Ten Hoeve J; UCLA Metabolomics Center, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA., Samad B; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA., Ironside AJ; Department of Pathology, Western General Hospital, NHS Lothian, Edinburgh, UK., di Magliano MP; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.; Department of Cell and Developmental Biology, Cancer Biology Program, University of Michigan, Ann Arbor, MI, USA., Muir A; Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA., Geiger R; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland., Combes AJ; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA.; Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Weaver VM; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA, USA. valerie.weaver@ucsf.edu.; Department of Bioengineering and Therapeutic Sciences and Department of Radiation Oncology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and The Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. valerie.weaver@ucsf.edu.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2024 Jul; Vol. 5 (7), pp. 1045-1062. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1038/s43018-024-00775-4
Abstrakt: Tumor progression is accompanied by fibrosis, a condition of excessive extracellular matrix accumulation, which is associated with diminished antitumor immune infiltration. Here we demonstrate that tumor-associated macrophages (TAMs) respond to the stiffened fibrotic tumor microenvironment (TME) by initiating a collagen biosynthesis program directed by transforming growth factor-β. A collateral effect of this programming is an untenable metabolic milieu for productive CD8 + T cell antitumor responses, as collagen-synthesizing macrophages consume environmental arginine, synthesize proline and secrete ornithine that compromises CD8 + T cell function in female breast cancer. Thus, a stiff and fibrotic TME may impede antitumor immunity not only by direct physical exclusion of CD8 + T cells but also through secondary effects of a mechano-metabolic programming of TAMs, which creates an inhospitable metabolic milieu for CD8 + T cells to respond to anticancer immunotherapies.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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