Amino acid metabolism in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 13, 2023

Abstract Amino acids are the building blocks of protein synthesis. They structural elements and energy sources cells necessary for normal cell growth, differentiation function. acid metabolism disorders have been linked with a number pathological conditions, including metabolic diseases, cardiovascular immune cancer. In case tumors, alterations in amino can be used not only as clinical indicators cancer progression but also therapeutic strategies. Since growth development tumors depend on intake foreign acids, more studies targeted tumor-related to selectively kill tumor cells. Furthermore, immune-related confirmed that regulates function effector T regulatory cells, affecting Therefore, studying associated disease identifying targets pathways may helpful treatment. This article mainly focuses research tumor-oriented reviews progress diseases related metabolism, order provide theoretical basis therapy metabolism.

Language: Английский

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Therapeutic targeting of tumour myeloid cells

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(4), P. 216 - 237

Published: Feb. 6, 2023

Language: Английский

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GM-CSF: A Double-Edged Sword in Cancer Immunotherapy

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 5, 2022

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that drives the generation of myeloid cell subsets including neutrophils, monocytes, macrophages, and dendritic cells in response to stress, infections, cancers. By modulating functions innate immune serve as bridge activate adaptive responses, GM-CSF globally impacts host surveillance under pathologic conditions. As with other soluble mediators immunity, too much or little has been found promote cancer aggressiveness. While prevents appropriate production subsequent activation anti-cancer can exhaust growth. The consequences signaling progression are function levels GM-CSF, type, tumor microenvironment. In this review, we first discuss secretion downstream receptor, GM-CSF’s role homeostasis. We then outline anti-tumorigenic pro-tumorigenic effects both on malignant non-malignant provide examples current clinical preclinical strategies harness potential while minimizing its deleterious effects. describe challenges achieving Goldilocks effect during administration GM-CSF-based therapies patients cancer. Finally, insights into how technologies map microenvironment spatially temporally may be leveraged intelligently for treatment malignancies.

Language: Английский

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Tumor-Associated Macrophages in Hepatocellular Carcinoma Pathogenesis, Prognosis and Therapy

Cancers, Journal Year: 2022, Volume and Issue: 14(1), P. 226 - 226

Published: Jan. 4, 2022

Hepatocellular carcinoma (HCC) constitutes a major health burden globally, and it is caused by intrinsic genetic mutations acting in concert with multitude of epigenetic extrinsic risk factors. Cancer induces myelopoiesis the bone marrow, as well mobilization hematopoietic stem progenitor cells, which reside spleen. Monocytes produced marrow spleen further infiltrate tumors, where they differentiate into tumor-associated macrophages (TAMs). The relationship between chronic inflammation hepatocarcinogenesis has been thoroughly investigated over past decade; however, several aspects role TAMs HCC development are yet to be determined. In response certain stimuli signaling, monocytes antitumor properties, classified M1-like. On other hand, under different polarization shifts towards an M2-like phenotype tumor promoting capacity. drive growth both directly indirectly, via suppression cytotoxic cell populations, including CD8+ T cells NK cells. microenvironment affects immunotherapies. Therefore, enhanced understanding its immunobiology essential for next-generation utilization various monocyte-centered anticancer treatment modalities clinical investigation, selectively targeting modulating processes monocyte recruitment, activation migration. This review summarizes current evidence on pathogenesis progression, their potential involvement therapy, shedding light emerging methods monocytes.

Language: Английский

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

Immunity, Journal Year: 2023, Volume and Issue: 56(1), P. 14 - 31

Published: Jan. 1, 2023

Language: Английский

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The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(7), P. 714 - 738

Published: May 19, 2023

Abstract Breast cancer is the most prevalent worldwide, and metastasis leading cause of death in patients. Human monocyte chemoattractant protein-1 (MCP-1/CCL2) was isolated from culture supernatants not only mitogen-activated peripheral blood mononuclear leukocytes but also malignant glioma cells based on its vitro chemotactic activity toward human monocytes. MCP-1 subsequently found to be identical a previously described tumor cell-derived factor thought responsible for accumulation tumor-associated macrophages (TAMs), it became candidate target clinical intervention; however, role TAMs development still controversial at time discovery MCP-1. The vivo progression first evaluated by examining tissues, including breast cancers. Positive correlations between level production tumors degree TAM infiltration were established. contribution growth primary lung, bone, brain examined mouse models. results these studies strongly suggested that promoter lung bone. Potential mechanisms microenvironment have been reported. In present manuscript, we review which attempt draw consensus discuss potential use as biomarker diagnosis.

Language: Английский

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Tumor-associated myeloid cells in cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: July 6, 2023

Tumor-associated myeloid cells (TAMCs) are among the most important immune cell populations in tumor microenvironment, and play a significant role on efficacy of checkpoint blockade. Understanding origin TAMCs was found to be essential determining their functional heterogeneity and, developing cancer immunotherapy strategies. While myeloid-biased differentiation bone marrow has been traditionally considered as primary source TAMCs, abnormal splenic hematopoietic stem progenitor cells, erythroid B precursor spleen, well embryo-derived have depicted origins TAMCs. This review article provides an overview literature with focus recent research progress evaluating origins. Moreover, this summarizes major therapeutic strategies targeting heterogeneous sources, shedding light implications for antitumor immunotherapies.

Language: Английский

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Cancer-Associated Adipocytes and Breast Cancer: Intertwining in the Tumor Microenvironment and Challenges for Cancer Therapy

Cancers, Journal Year: 2023, Volume and Issue: 15(3), P. 726 - 726

Published: Jan. 24, 2023

Adipocytes are the main components in breast tissue, and cancer-associated adipocytes (CAAs) one of most important tumor microenvironment cancer (BC). Bidirectional regulation was found between CAAs BC cells. facilitates dedifferentiation adjacent to form with morphological biological changes. increase secretion multiple cytokines adipokines promote tumorigenesis, progression, metastasis by remodeling extracellular matrix, changing aromatase expression, metabolic reprogramming, shaping immune microenvironment. also associated therapeutic response provide potential targets therapy. The present review provides a comprehensive description crosstalk discusses strategies target overcome treatment resistance.

Language: Английский

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FFAR2 expressing myeloid-derived suppressor cells drive cancer immunoevasion

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Feb. 24, 2024

Abstract Background Emerging evidences suggest that aberrant metabolites contributes to the immunosuppressive microenvironment leads cancer immune evasion. Among tumor cells, myeloid-derived suppressor cells (MDSCs) are pathologically activated and extremely immunosuppressive, which closely associated with poor clinical outcomes of patients. However, correlation between MDSCs mediated immunosuppression particular metabolism remained elusive. Methods Spontaneous lung adenocarcinoma subcutaneous mouse models, gas chromatography–mass spectrometry (GC–MS) immunofluorescence assay patient-derived tissues, flow cytometry, RNA sequencing Western blotting were utilized. Results Metabolite profiling revealed a significant accumulation acetic acids in tissues from both patients model, contribute suppression progression significantly through free fatty acid receptor 2 (FFAR2). Furthermore, FFAR2 is highly expressed (LUAD) greatly prognosis. Surprisingly, whole or myeloid Ffar2 gene deletion markedly inhibited urethane-induced carcinogenesis syngeneic growth reduced increased CD8 + T cell infiltration. Mechanistically, deficiency expression Arg1 Gαq/Calcium/PPAR-γ axis, eliminated dysfunction relieving L-Arginine consumption microenvironment. Therefore, replenishment inhibition PPAR-γ restored acids/FFAR2 significantly. Finally, overcame resistance checkpoint blockade enhancing recruitment cytotoxicity tumor-infiltrating cells. Conclusion Altogether, our results demonstrate axis enhances Gαq/calcium/PPAR-γ/Arg1 signaling pathway, thus contributing progression. may serve as potential new target eliminate reverse microenvironment, has great improving immunotherapy.

Language: Английский

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Metabolic Reprogramming of Neutrophils in the Tumor Microenvironment: Emerging Therapeutic Targets

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217466 - 217466

Published: Jan. 1, 2025

Language: Английский

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