Control of tumor-associated macrophage responses by nutrient acquisition and metabolism

Zhang, Xian; Ji, Liangliang; Li, Ming O.

doi:10.1016/j.immuni.2022.12.003

Cited by 50 publications

(18 citation statements)

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“…For example, the transferrin receptor (TFRC), a transmembrane protein present on the plasma membrane, interacts with transferrin (which is bound to iron) and generally initiates endocytosis . CD36 plays crucial roles in macrophage differentiation and lipid accumulation and supports tumor growth. , The secreted protein Ifi35 had been reported to promote proliferation and cytotoxic activity of both primary CD8 + T cells and CAR-T cells through the PI3K/AKT/mTOR signaling pathway in colorectal cancer . In this study, TRFC and CD36 were upregulated, but Ifi35 was downregulated in tumor progression.…”

Section: Resultsmentioning

confidence: 70%

“…22 CD36 plays crucial roles in macrophage differentiation and lipid accumulation and supports tumor growth. 16,23 The secreted protein Ifi35 had been reported to promote proliferation and cytotoxic activity of both primary CD8 + T cells and CAR-T cells through the PI3K/AKT/mTOR signaling pathway in colorectal cancer. 24 In this study, TRFC and CD36 were upregulated, but Ifi35 was downregulated in tumor progression.…”

Section: Dynamic Phenotypes Of Tams and Mons In A Progression-depende...mentioning

confidence: 99%

“…Using comprehensive proteomics analysis, we found that glycolysis metabolism reprogramming may play an important role in TAM differentiation, 14 which are confirmed by subsequent studies. 15,16 An ex vivo cell culture model, tumorextract-stimulated bone marrow-derived macrophages (TES-BMDMs), was used to mimic TAMs in vitro. 14 About 1e7 TES-BMDMs per sample (>50 μg of protein) were prepared for filteraided sample preparation (FASP), followed by mass spectrometry detection.…”

Section: ■ Introductionmentioning

confidence: 99%

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Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-Associated Macrophages and Their Precursor Cells in Tumor Progression

Liu,

Liu

et al. 2024

J. Proteome Res.

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Tumor-associated macrophages (TAMs) are key regulators in tumor progression, but the precise role of bone marrow-derived monocytes (Mons) as TAM precursors and their dynamic phenotypes regulated by the tumor microenvironment (TME) remain unclear. Here, we developed an optimized microproteomics workflow to analyze lowcell-number mouse myeloid cells. We sorted TAMs and their corresponding Mons (1 × 10 5 per sample) from individual melanoma mouse models at both the early and late stages. We established the protein expression profiles for these cells by mass spectrometry. Subsequently, we analyzed the dynamics phenotypes of TAMs and identified a characteristic protein expression profile characterized by upregulated cholesterol metabolism and downregulated immune responses during tumor progression. Moreover, we found the downregulation of both STAT5 and PYCARD expression not only in late-stage TAMs but also in late-stage Mons, indicating a loss of the ability to induce inflammatory responses prior to Mons infiltration into TME. Taken together, our study provides valuable insights into the progression-dependent transitions between TAMs and their precursor cells, as well as the cross-organ communications of tumor and bone marrow.

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Section: Resultsmentioning

confidence: 70%

Section: Dynamic Phenotypes Of Tams and Mons In A Progression-depende...mentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-Associated Macrophages and Their Precursor Cells in Tumor Progression

Liu,

Liu

et al. 2024

J. Proteome Res.

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“…17 These phenomena demonstrate that 1C metabolism enables the mediation of antitumour immune responses by metabolic and nutrient sensing machinery. 18 Therefore, methods that interfere with 1C metabolism provide a hopeful scheme for improving the application of immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Targeting one‐carbon metabolism for cancer immunotherapy

Ren,

Wang,

Zheng

et al. 2024

Clinical & Translational Med

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BackgroundOne‐carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic pathways, including nucleotide metabolism, amino acid metabolism, cellular redox defence and epigenetic maintenance. At present, 1C metabolism is considered the hallmark of cancer. The 1C units obtained from the metabolic pathways increase the proliferation rate of cancer cells. In addition, anticancer drugs, such as methotrexate, which target 1C metabolism, have long been used in the clinic. In terms of immunotherapy, 1C metabolism has been used to explore biomarkers connected with immunotherapy response and immune‐related adverse events in patients.MethodsWe collected numerous literatures to explain the roles of one‐carbon metabolism in cancer immunotherapy.ResultsIn this review, we focus on the important pathways in 1C metabolism and the function of 1C metabolism enzymes in cancer immunotherapy. Then, we summarise the inhibitors acting on 1C metabolism and their potential application on cancer immunotherapy. Finally, we provide a viewpoint and conclusion regarding the opportunities and challenges of targeting 1C metabolism for cancer immunotherapy in clinical practicability in the future.ConclusionTargeting one‐carbon metabolism is useful for cancer immunotherapy.

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“…For example, in the bone, metastatic cancer cells hijack osteoclasts to induce bone resorption to establish a tumor-supportive niche (35). Metabolic adaptations of TAMs have been well characterized in tumors (38), but there is a need to better understand more specifically how their metabolic status is influenced by their tissue of origin and the metabolic demands of their transformed 'client' cells. We hypothesize that tumor cell co-option of homeostatic TRM relationships, including their metabolic relationships, can expose targetable vulnerabilities for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

EGFR⁺lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth

Kuhlmann-Hogan

Cordes

et al. 2023

Preprint

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The limited efficacy of currently approved immunotherapies in EGFR-mutant lung adenocarcinoma (LUAD) underscores the need to better understand mechanisms governing local immunosuppression. Elevated surfactant and GM-CSF secretion from the transformed epithelium induces tumor-associated alveolar macrophages (TA-AM) to proliferate and support tumor growth by rewiring inflammatory functions and lipid metabolism. TA-AM properties are driven by increased GM-CSF-PPARg; signaling and inhibition of airway GM-CSF or PPARg; in TA-AMs suppresses cholesterol efflux to tumor cells, which impairs EGFR phosphorylation and restrains LUAD progression. In the absence of TA-AM metabolic support, LUAD cells compensate by increasing cholesterol synthesis, and blocking PPARg; in TA-AMs simultaneous with statin therapy further suppresses tumor progression and increases T cell effector functions. These results reveal new therapeutic combinations for immunotherapy resistant EGFR-mutant LUADs and demonstrate how such cancer cells can metabolically co-opt TA-AMs through GM-CSF-PPARg; signaling to provide nutrients that promote oncogenic signaling and growth.

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Control of tumor-associated macrophage responses by nutrient acquisition and metabolism

Cited by 50 publications

References 213 publications

Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-Associated Macrophages and Their Precursor Cells in Tumor Progression

Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-Associated Macrophages and Their Precursor Cells in Tumor Progression

Targeting one‐carbon metabolism for cancer immunotherapy

EGFR⁺lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth

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Control of tumor-associated macrophage responses by nutrient acquisition and metabolism

Cited by 50 publications

References 213 publications

Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-Associated Macrophages and Their Precursor Cells in Tumor Progression

Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-Associated Macrophages and Their Precursor Cells in Tumor Progression

Targeting one‐carbon metabolism for cancer immunotherapy

EGFR+lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth

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EGFR⁺lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth