Implications of metabolism-driven myeloid dysfunctions in cancer therapy.
Cancer therapy
Metabolism
Myeloid-derived suppressor cells
Myelopoiesis
Tumor-associated macrophages
Journal
Cellular & molecular immunology
ISSN: 2042-0226
Titre abrégé: Cell Mol Immunol
Pays: China
ID NLM: 101242872
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
31
05
2020
accepted:
10
09
2020
pubmed:
21
10
2020
medline:
28
12
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
Immune homeostasis is maintained by an adequate balance of myeloid and lymphoid responses. In chronic inflammatory states, including cancer, this balance is lost due to dramatic expansion of myeloid progenitors that fail to mature to functional inflammatory neutrophils, macrophages, and dendritic cells (DCs), thus giving rise to a decline in the antitumor effector lymphoid response. Cancer-related inflammation orchestrates the production of hematopoietic growth factors and cytokines that perpetuate recruitment and activation of myeloid precursors, resulting in unresolved and chronic inflammation. This pathologic inflammation creates profound alterations in the intrinsic cellular metabolism of the myeloid progenitor pool, which is amplified by competition for essential nutrients and by hypoxia-induced metabolic rewiring at the tumor site. Therefore, persistent myelopoiesis and metabolic dysfunctions contribute to the development of cancer, as well as to the severity of a broad range of diseases, including metabolic syndrome and autoimmune and infectious diseases. The aims of this review are to (1) define the metabolic networks implicated in aberrant myelopoiesis observed in cancer patients, (2) discuss the mechanisms underlying these clinical manifestations and the impact of metabolic perturbations on clinical outcomes, and (3) explore new biomarkers and therapeutic strategies to restore immunometabolism and differentiation of myeloid cells towards an effector phenotype to increase host antitumor immunity. We propose that the profound metabolic alterations and associated transcriptional changes triggered by chronic and overactivated immune responses in myeloid cells represent critical factors influencing the balance between therapeutic efficacy and immune-related adverse effects (irAEs) for current therapeutic strategies, including immune checkpoint inhibitor (ICI) therapy.
Identifiants
pubmed: 33077904
doi: 10.1038/s41423-020-00556-w
pii: 10.1038/s41423-020-00556-w
pmc: PMC7570408
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
829-841Références
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