The metabolic cross-talk between cancer and T cells

Miguel, Silvia Cadenas-De; Lucianer, Giulia; Elia, Ilaria

doi:10.1016/j.tibs.2023.03.004

Cited by 4 publications

(1 citation statement)

References 116 publications

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“…Tumor cells can consume large amounts of glucose and amino acids, depriving nearby immune cells of these essential nutrients necessary for their activation and effector functions. Nutrient competition within the TME can impair the function of immune cells, including T cells and antigen-presenting cells (APCs), leading to reduced antitumor immune responses and immune evasion by the tumor [48][49][50].…”

Section: Metabolic Competitionmentioning

confidence: 99%

Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment: Unraveling Molecular Pathways, Immunometabolic Processes, and Their Significance in Immunotherapy for Hepatocellular Carcinoma (HCC)

Chu,

2024

Macrophages - Molecular Pathways and Immunometabolic Processes [Working Title]

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Hepatocellular carcinoma (HCC) is a major global health concern, and understanding the complex interplay of immune cells within the tumor microenvironment is crucial. This review explores the roles of myeloid-derived suppressor cells (MDSCs) and macrophages in HCC, focusing on their molecular pathways, immunometabolic processes, and implications for immunotherapy. We begin by elucidating the origin, expansion, and immunosuppressive mechanisms of MDSCs, emphasizing the importance of molecular pathways and immunometabolism in regulating their functions. In parallel, we delve into the dual nature of tumor-associated macrophages (TAMs) and discuss the molecular and metabolic cues governing their plasticity. Tumor metabolism is a central theme, with a comprehensive overview of altered metabolic processes in cancer cells and their impact on immune cells in the tumor microenvironment. We examine the metabolic crosstalk between tumor cells, MDSCs, and macrophages, shedding light on how tumor metabolism contributes to immune evasion. Furthermore, we discuss the challenges and limitations faced in the clinical application of immunotherapy in HCC. In conclusion, this review highlights the intricate web of molecular pathways and immunometabolic processes shaping the functions of MDSCs and macrophages in HCC. Understanding these dynamics is essential for the innovative immunotherapeutic interventions in HCC, improving outcomes of this devastating disease.

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Section: Metabolic Competitionmentioning

confidence: 99%

Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment: Unraveling Molecular Pathways, Immunometabolic Processes, and Their Significance in Immunotherapy for Hepatocellular Carcinoma (HCC)

Chu,

2024

Macrophages - Molecular Pathways and Immunometabolic Processes [Working Title]

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Contact-based thymidylate transfer promotes collective tumor growth

Siddiqui,

Rømer,

Pinna

et al. 2024

Preprint

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SummarySustained cell proliferation is a fundamental hallmark of cancer, yet its mechanism remains elusive, particularly in context of intercellular cooperation and metabolite exchange. We uncover a mechanism of tumor growth via collective proliferation, where a syncytium of cells connected by gap junctions allows dTMP equilibration and dispenses ubiquitous activation of canonical dTMP biosynthesis and salvage driven by thymidylate synthase (TYMS) and thymidine kinase 1 (TK1) respectively. Collective proliferation is observed in vitro and in clinical samples, and it is validated in a genetic mouse model of lung cancer harboring dualTyms/Tk1tumor-specific knockout, in which cells propel tumor progression despite lacking enzymatic dTMP synthesis, and the tumor growth is significantly mitigated by gap junction inhibition. These findings suggest that a programmed dTMP equilibration sustains collective tumor growth and revises the current dogma of a ubiquitous de novo activation. This mechanism could be exploited in cancer therapy.

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Construction of a mitochondria genes-based model for prognosis prediction, drug guidance and immune feature analysis in ovarian serous cystadenocarcinoma

Shen

Ding

et al. 2023

Preprint

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Background Ovarian serous cystadenocarcinoma (OSC) is the most common pathological subtype of ovarian cancer (OC) associated with high mortality. Albeit dysregulated mitochondrial metabolism has been implicated with OC, the role of mitochondrial genes in OSC remains unclear. We sought to construct a model based on mitochondrial genes for prognosis prediction, drug guidance and immune feature analysis of OSC. Methods Differentially expressed genes (DEGs) and mitochondrial-related DEGs (MRGs) were identified through the Cancer Genome Atlas (TCGA)-OV dataset. Consensus clustering algorithm was applied to classify OSC patients into distinct MRGs subtypes. Prognosis-related MRGs were screened to construct the prognosis-related Risk score model, which was verified using GSE26193 dataset and immunohistochemistry (IHC) score model based on staining intensity and extent scores of MRGs. A visualized nomogram was developed to predict 1-, 3- and 5-year overall survival (OS) and drug response. The correlation of MRGs subtypes with risk subgroups and the association of Risk score model with immune response and infiltration were also investigated. Results 341 MRGs were identified from TCGA-OV, and OSC patients could be mainly divided into two MRGs subtypes. A novel prognostic Risk score model based on 7-MRGs, including ACOT13, ACSS3, COA6, HINT2, MRPL14, NDUFC2 and NDUFV2, was developed and validated via GSE26193 dataset and IHC score model. Patients in the low-risk group had a significantly longer OS. The nomogram exhibited good prognostic assessment accuracy in both training and validation datasets. Drug sensitivity analysis indicated that cisplatin, paclitaxel and docetaxel were more sensitive in the low-risk group; VEGFR inhibitor Axitinib, and BRAF inhibitors Vemurafenib and SB590885 showed better sensitivity in the high-risk group; moreover, patients in the low-risk group could have better anti-PD-1 immunotherapy response. Patients in “cluster1” MRGs subtype had lower risk scores and better immunotherapy response scores than the “cluster2” subgroup. More significant infiltrated tumor killing cells (CD8+ T cells) and higher M1 / M2 macrophage ratio were in “cluster1” patients. Conclusions Our novel 7 MRGs-based Risk score model has huge prospects to evaluate the prognosis and guide drug treatment. The favorable prognosis associated with the low-risk group is closely related to better immune response and more significant anti-tumor cellular infiltration.

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The metabolic cross-talk between cancer and T cells

Cited by 4 publications

References 116 publications

Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment: Unraveling Molecular Pathways, Immunometabolic Processes, and Their Significance in Immunotherapy for Hepatocellular Carcinoma (HCC)

Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment: Unraveling Molecular Pathways, Immunometabolic Processes, and Their Significance in Immunotherapy for Hepatocellular Carcinoma (HCC)

Contact-based thymidylate transfer promotes collective tumor growth

Construction of a mitochondria genes-based model for prognosis prediction, drug guidance and immune feature analysis in ovarian serous cystadenocarcinoma

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