The Metabolic Control of Myeloid Cells in the Tumor Microenvironment

Ramel, Eloise; Lillo, Sebastian; Daher, Boutaina; Fioleau, Marina; Daubon, Thomas; Saleh, Maya

doi:10.3390/cells10112960

Cited by 5 publications

(3 citation statements)

References 98 publications

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“…The various states of polarization, activation and regulation of myeloid cells are accompanied by adaptation of lipid metabolism [ 14 , 15 ]. In contract, lipid metabolism modulates the activity of these cells [ 16 ].…”

Section: Lipid Metabolism In Myeloid Cellsmentioning

confidence: 99%

Impact of Lipid Metabolism on Antitumor Immune Response

Mabrouk

Lecoeur

Bettaı̈eb

et al. 2022

Cancers

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Over the past decade, metabolic reprogramming has been defined as a hallmark of cancer. More recently, a large number of studies have demonstrated that metabolic reprogramming can modulate the differentiation and functions of immune cells, and thus modify the antitumor response. Increasing evidence suggests that modified energy metabolism could be responsible for the failure of antitumor immunity. Indeed, tumor-infiltrating immune cells play a key role in cancer, and metabolic switching in these cells has been shown to help determine their phenotype: tumor suppressive or immune suppressive. Recent studies in the field of immunometabolism focus on metabolic reprogramming in the tumor microenvironment (TME) by targeting innate and adaptive immune cells and their associated anti- or protumor phenotypes. In this review, we discuss the lipid metabolism of immune cells in the TME as well as the effects of lipids; finally, we expose the link between therapies and lipid metabolism.

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Section: Lipid Metabolism In Myeloid Cellsmentioning

confidence: 99%

Impact of Lipid Metabolism on Antitumor Immune Response

Mabrouk

Lecoeur

Bettaı̈eb

et al. 2022

Cancers

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“…Immune cells need to adapt to the challenges imposed by the TME, such as insufficient nutrients and oxygen. These conditions eventually impact their survival and functionality and are often linked to the acquisition of pro-tumorigenic properties (Strauss et al, 2021 ; Ramel et al, 2021 ). For instance, positron emission tomography imaging has shown that myeloid cells in tumors consume high amounts of glucose (Reinfeld et al, 2021 ), and our previous research demonstrated that TANs rely on increased glucose metabolism to survive in the TME and differentiate into tumor-promoting SiglecF + cells (Ancey et al, 2021 a).…”

Section: Discussionmentioning

confidence: 99%

Bcl-xL targeting eliminates ageing tumor-promoting neutrophils and inhibits lung tumor growth

Bodac,

Mayet,

Rana

et al. 2023

EMBO Mol Med

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Elevated peripheral blood and tumor-infiltrating neutrophils are often associated with a poor patient prognosis. However, therapeutic strategies to target these cells are difficult to implement due to the life-threatening risk of neutropenia. In a genetically engineered mouse model of lung adenocarcinoma, tumor-associated neutrophils (TAN) demonstrate tumor-supportive capacities and have a prolonged lifespan compared to circulating neutrophils. Here, we show that tumor cell-derived GM-CSF triggers the expression of the anti-apoptotic Bcl-xL protein and enhances neutrophil survival through JAK/STAT signaling. Targeting Bcl-xL activity with a specific BH3 mimetic, A-1331852, blocked the induced neutrophil survival without impacting their normal lifespan. Specifically, oral administration with A-1331852 decreased TAN survival and abundance, and reduced tumor growth without causing neutropenia. We also show that G-CSF, a drug used to combat neutropenia in patients receiving chemotherapy, increased the proportion of young TANs and augmented the anti-tumor effect resulting from Bcl-xL blockade. Finally, our human tumor data indicate the same role for Bcl-xL on pro-tumoral neutrophil survival. These results altogether provide preclinical evidence for safe neutrophil targeting based on their aberrant intra-tumor longevity.

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“…Currently, an increasing number of studies have focused on the clinical therapeutic effects of ATRA and have reported its role in downregulating the proportions of MDSCs and promoting their maturation; however, no evidence has shown that ATRA can directly reprogram the cytokine expression profiles of MDSCs. The metabolic regulation of MDSCs has emerged as a critical modulator in the suppressive tumor environment ( 42 ). ATRA can regulate amino acid and fatty acid metabolism ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Combining all-trans retinoid acid treatment targeting myeloid-derived suppressive cells with cryo-thermal therapy enhances antitumor immunity in breast cancer

et al. 2022

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Targeting myeloid-derived suppressive cells (MDSCs) has been considered a potential strategy in tumor therapy. However, a single drug targeting MDSCs remains a challenge in the clinic. An increasing number of studies have shown that combination agents targeting MDSCs and immunotherapy may provide exciting new insights and avenues to explore in tumor therapy. In our previous study, a novel cryo-thermal therapy was developed for metastatic tumors that systematically activate innate and adaptive immunity. Moreover, cryo-thermal therapy was shown to dramatically decrease the levels of MDSCs and induce their differentiation toward potent antigen-presenting cells. However, the therapeutic effects of cryo-thermal therapy on the 4T1 mouse breast cancer model were still not satisfactory because of the high level of MDSCs before and after treatment. Therefore, in this study, we combined cryo-thermal therapy with all-trans retinoid acid (ATRA), a small molecule drug that can induce the inflammatory differentiation of MDSCs. We found that combination therapy notably upregulated the long-term survival rate of mice. Mechanically, combination therapy promoted the phenotype and functional maturation of MDSCs, efficiently decreasing suppressive molecule expression and inhibiting glutamine and fatty acid metabolism. Moreover, MDSCs at an early stage after combination therapy significantly decreased the proportions of Th2 and Treg subsets, which eventually resulted in Th1-dominant CD4+ T-cell differentiation, as well as enhanced cytotoxicity of CD8+ T cells and natural killer cells at the late stage. This study suggests a potential therapeutic strategy for combination ATRA treatment targeting MDSCs with cryo-thermal therapy to overcome the resistance of MDSC-induced immunosuppression in the clinic.

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The Metabolic Control of Myeloid Cells in the Tumor Microenvironment

Cited by 5 publications

References 98 publications

Impact of Lipid Metabolism on Antitumor Immune Response

Impact of Lipid Metabolism on Antitumor Immune Response

Bcl-xL targeting eliminates ageing tumor-promoting neutrophils and inhibits lung tumor growth

Combining all-trans retinoid acid treatment targeting myeloid-derived suppressive cells with cryo-thermal therapy enhances antitumor immunity in breast cancer

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