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Macrophages

Specialization determines outcomes in inflammation and cancer

Nature Immunology volume 24, pages 1399–1401 (2023)Cite this article

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The functional heterogeneity of macrophages has ontological and microenvironmental bases, and differentially affects pathology. In pancreatitis, tissue-resident macrophages promote protective fibrosis that favors the maintenance of pancreatic homeostasis. In pancreatic ductal adenocarcinoma, they promote tumor progression by facilitating stromal desmoplasia.

Macrophage functions can also evolve dynamically under the control of cell-intrinsic mechanisms, as observed during the spontaneous recovery of homeostatic functions in macrophages undergoing lipopolysaccharide-mediated tolerance5. During tumor development, dynamic adaptation of macrophage functions may also occur in conjunction with the remodeling of tumor microphysiology (with changing oxygen availability, pH, glucose levels, amino acids, lipid metabolism and inflammatory signals), and as a result of hematopoietic changes (for example, emergency hematopoiesis) that influence the differentiation and availability of myeloid progenitors6. Growing interest in the mechanisms that drive this functional heterogeneity underscores its relevance in both physiology and pathology, fueling efforts to therapeutically re-educate macrophage functions7.

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Fig. 1: Beneficial versus detrimental roles of tissue-resident macrophages in different disease contexts.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Piemonte Orientale ‘A. Avogadro’, Novara, Italy

    Antonio Sica

  2. Humanitas Clinical and Research Center, Istituto di Ricovero e Cura a Carattere Scientifico, Rozzano, Milan, Italy

    Antonio Sica

  3. Department of Urology, Humanitas Research Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rozzano, Milan, Italy

    Massimo Lazzeri

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  1. Antonio Sica
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  2. Massimo Lazzeri
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Correspondence to Antonio Sica.

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The authors declare no competing interests.

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Sica, A., Lazzeri, M. Specialization determines outcomes in inflammation and cancer. Nat Immunol 24, 1399–1401 (2023). https://doi.org/10.1038/s41590-023-01592-0

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  • DOI: https://doi.org/10.1038/s41590-023-01592-0

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