Modulating NK cell metabolism for cancer immunotherapy

Terrén, Íñigo; Orrantia, Ane; Vitallé, Joana; Astarloa-Pando, Gabirel; Zenarruzabeitia, Olatz; Borrego, Francisco

doi:10.1053/j.seminhematol.2020.10.003

Cited by 25 publications

(22 citation statements)

References 156 publications

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“…It was found that genes related to glycolysis and OXPHOS were downregulated in NK cells undergoing severe TME. By contrast, the activity of lipid metabolism is increased (96,97). Studies have also confirmed that when NK cells survival is threatened, lipid metabolism becomes the preferred mode of metabolism (98,99).…”

Section: Influence Of Lactic Acid and Hypoxia On The Nk Cell Phenotypementioning

confidence: 95%

Metabolic heterogeneity and immunocompetence of infiltrating immune cells in the breast cancer microenvironment (Review)

et al. 2021

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Breast cancer is one of the most common malignancies in women and is characterized by active immunogenicity. Immune cell infiltration plays an important role in the development of breast cancer. The degree of infiltration influences both the response to and effect of treatment. However, immune infiltration is a complex process. Differences in oxygen partial pressure, blood perfusion and nutrients in the tumor microenvironment (TME) suggest that infiltrating immune cells in different sites experience different microenvironments with corresponding changes in the metabolic mode, that is, immune cell metabolism is heterogenous in the TME. Furthermore, the present review found that lipid metabolism can support the immunosuppressive microenvironment in breast cancer based on a review of published literature. Research in this field is still ongoing; however, it is vital to understand the metabolic patterns and effects of different microenvironments for antitumor therapy. Therefore, this review discusses the metabolic responses of various immune cells to different microenvironments in breast cancer and provides potentially meaningful insights for tumor immunotherapy.

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Section: Influence Of Lactic Acid and Hypoxia On The Nk Cell Phenotypementioning

confidence: 95%

Metabolic heterogeneity and immunocompetence of infiltrating immune cells in the breast cancer microenvironment (Review)

et al. 2021

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“…The development of immune memory is related to the greater cytotoxicity of memory NK cells upon repeated contact with the antigen [ 22 ]. In addition, the studies on the influence of changes in NK cell metabolism on their activity seem to be of great interest [ 23 ]. It has been known for many years that the use of certain immunosuppressants alters the metabolism of T cells and affects their activity and differentiation.…”

Section: Nk (Natural Killer Cells)mentioning

confidence: 99%

KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease

Dębska-Zielkowska

Moszkowska

Zieliński

et al. 2021

Cells

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Natural killer (NK) cells are part of the cellular immune response. They target mainly cancer and virally infected cells. To a high extent cytotoxic activity of NK cells is regulated inter alia by signals from killer immunoglobulin-like receptors (KIR). The major histocompatibility complex (MHC) class I molecules are important ligands for KIR receptors. Binding of ligands (such as MHC I) to the KIR receptors has the important role in solid organ or hematopoietic cell transplantation. Of note, the understanding of the relationship between KIR and MHC receptors may contribute to the improvement of transplant results. Donor-recipient matching, which also includes the KIR typing, may improve monitoring, individualize the treatment and allow for predicting possible effects after transplantation, such as the graft-versus-leukemia effect (GvL) or viral re-infection. There are also less evident implications of KIR/MHC matching, such as with pregnancy and cancer. In this review, we present the most relevant literature reports on the importance of the KIR/MHC relationship on NK cell activity and hematopoietic stem cell transplantation (HSCT)/solid organ transplantation (SOT) effects, the risk of allograft rejection, protection against post-transplant cytomegalovirus (CMV) infection, pregnancy complications, cancer and adoptive therapy with NK cells.

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“…Mature resting NK cells use OXPHOS to supply their homeostatic requirements [76,77]. In response to cytokines such as IL-2, IL-12, IL-15, and IL-18, activated NK cells increase both glycolysis and OXPHOS pathways to fuel biosynthetic precursors, necessary for proliferation and effector functions [78]. Indeed, OXPHOS pathway inhibition in NK cells correlates with a significant decrease in IFNγ secretion and cytotoxic activities [78].…”

Section: Nk Cell Metabolismmentioning

confidence: 99%

“…In the developmental process of NK cells, as far as during the process of education, a shift towards a more glycolytic metabolic profile is observed. Several studies have yet to comprehensively measure the metabolic activity of NK cells at different stages of development [78]. Recently, it was elucidated that metabolic rewiring in NK cells activated by IL-12, IL-15 and IL-18 depends on three master regulators: TORC1, a signal transducer, SREBP and cMYC acting as transcriptional factors [76,[79][80][81].…”

Section: Nk Cell Metabolismmentioning

confidence: 99%

Metabolic Rewiring in the Tumor Microenvironment to Support Immunotherapy: A Focus on Neutrophils, Polymorphonuclear Myeloid-Derived Suppressor Cells and Natural Killer Cells

et al. 2021

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Leukocytes often undergo rapid changes in cell phenotype, for example, from a resting to an activated state, which places significant metabolic demands on the cell. These rapid changes in metabolic demand need to be tightly regulated to support immune cell effector functions during the initiation and downregulation of an immune response. Prospects for implementing cancer immunotherapy also rest on the idea of optimizing the metabolic profile of immune cell effectors. Here, we examine this issue by focusing on neutrophils and NK cells as cells of increasing interest in cancer immunology and tumor immunometabolism, because they can be targeted or, in the case of NK, used as effectors in immunotherapy. In addition, neutrophils and NK cells have been shown to functionally interact. In the case of neutrophils, we also extended our interest to polymorphonuclear MDSC (PMN-MDSCs), since the granulocytic subset of MDSCs share many phenotypes and are functionally similar to pro-tumor neutrophils. Finally, we reviewed relevant strategies to target tumor metabolism, focusing on neutrophils and NK cells.

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Modulating NK cell metabolism for cancer immunotherapy

Cited by 25 publications

References 156 publications

Metabolic heterogeneity and immunocompetence of infiltrating immune cells in the breast cancer microenvironment (Review)

Metabolic heterogeneity and immunocompetence of infiltrating immune cells in the breast cancer microenvironment (Review)

KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease

Metabolic Rewiring in the Tumor Microenvironment to Support Immunotherapy: A Focus on Neutrophils, Polymorphonuclear Myeloid-Derived Suppressor Cells and Natural Killer Cells

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