New Immunometabolic Strategy Based on Cell Type-Specific Metabolic Reprogramming in the Tumor Immune Microenvironment

Sung, Ji‐Yong; Cheong, Jae‐Ho

doi:10.3390/cells11050768

Cited by 21 publications

(11 citation statements)

References 167 publications

(188 reference statements)

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“…Besides, sufficient supply of glucose and glutamine are vital metabolite nutrition required for T cell differentiation and function. However, cancer cells would compete for glucose and glutamine intake from T cells to enhance their growth and proliferation ( 51 – 53 ). ICI therapy is based on the properties of T cells targeting therapeutic checkpoints, such as PD1.…”

Section: Discussionmentioning

confidence: 99%

Identification of cuproptosis-related subtypes, cuproptosis-related gene prognostic index in hepatocellular carcinoma

Liu

et al. 2022

Front. Immunol.

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Cuproptosis is a novel form of cell death, correlated with the tricarboxylic acid (TCA) cycle. However, the metabolic features and the benefit of immune checkpoint inhibitor (ICI) therapy based on cuproptosis have not yet been elucidated in Hepatocellular carcinoma (HCC). First, we identified and validated three cuproptosis subtypes based on 10 cuproptosis-related genes (CRGs) in HCC patients. We explored the correlation between three cuproptosis subtypes and metabolism-related pathways. Besides, a comprehensive immune analysis of three cuproptosis subtypes was performed. Then, we calculated the cuproptosis-related gene prognostic index (CRGPI) score for predicting prognosis and validated its predictive capability by Decision curve analysis (DCA). We as well explored the benefit of ICI therapy of different CRGPI subgroups in two anti-PD1/PD-L1 therapy cohorts (IMvigor210 cohort and GSE176307). Finally, we performed the ridge regression algorithm to calculate the IC50 value for drug sensitivity and Gene set enrichment analysis (GSEA) analysis to explore the potential mechanism. We found that cluster A presented a higher expression of FDX1 and was correlated with metabolism, glycolysis, and TCA cycle pathways, compared with the other two clusters. HCC patients with high CRGPI scores had a worse OS probability, and we further found that the CRGPI-high group had high expression of PD1/PDL1, TMB, and better response (PR/CR) to immunotherapy in the IMvigor210 cohort and GSE176307. These findings highlight the importance of CRGPI serving as a potential biomarker for both prognostic and immunotherapy for HCC patients. Generally, our results provide novel insights about cuproptosis into immune therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Identification of cuproptosis-related subtypes, cuproptosis-related gene prognostic index in hepatocellular carcinoma

Liu

et al. 2022

Front. Immunol.

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“…Telomere maintenance is essential for cancer cell survival and proliferation [ 31 ]. However, our study demonstrates that cancer cells maintain their own survival and proliferation by changing and using the cancer microenvironment [ 32 ] to their advantage, even where TMM is absent. We defined four types of TMM, but the current knowledge about the NDTMM type in GC is sparse.…”

Section: Discussionmentioning

confidence: 99%

Single Cell Analysis of Gastric Cancer Reveals Non-Defined Telomere Maintenance Mechanism

Sung

Cheong

2022

Cells

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Telomere maintenance mechanisms (TMMs) are important for cell survival and homeostasis. However, most related cancer research studies have used heterogenous bulk tumor tissue, which consists of various single cells, and the cell type properties cannot be precisely recognized. In particular, cells exhibiting non-defined TMM (NDTMM) indicate a poorer prognosis than those exhibiting alternative lengthening of telomere (ALT)-like mechanisms. In this study, we used bioinformatics to classify TMMs by cell type in gastric cancer (GC) in single cells and compared the biological processes of each TMM. We elucidated the pharmacological vulnerabilities of NDTMM type cells, which are associated with poor prognosis, based on molecular mechanisms. We analyzed differentially expressed genes in cells exhibiting different TMMs in two single-cell GC cohorts and the pathways enriched in single cells. NDTMM type cells showed high stemness, epithelial–mesenchymal transition, cancer hallmark activity, and metabolic reprogramming with mitochondrial abnormalities. Nuclear receptor subfamily 4 group A member 1 (NR4A1) activated parkin-dependent mitophagy in association with tumor necrosis factor-alpha (TNFA) to maintain cellular homeostasis without TMM. NR4A1 overexpression affected TNFA-induced GC cell apoptosis by inhibiting Jun N-terminal kinase/parkin-dependent mitophagy. Our findings also revealed that NR4A1 is involved in cell cycle mediation, inflammation, and apoptosis to maintain cell homeostasis, and is a novel potential therapeutic target in recalcitrant GC.

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“…Several cells of the immune system, likely cancer cells, might implement a metabolic reprograming. Both anaerobic glycolysis and glutamine metabolizing are often used instead of OxoPhos in various immune cells to obtain energy [ 44 ]. This switch in immune cells favors anabolic reactions such as the biosynthesis of fatty acids, proteins, and nucleotides in order to provide rapid growth and cell division.…”

Section: Interplay Between Metabolic Shift and Immune Responsementioning

confidence: 99%

Cancer Cell Metabolism Reprogramming and Its Potential Implications on Therapy in Squamous Cell Carcinoma of the Head and Neck: A Review

Perri¹,

Scarpati²,

Pontone³

et al. 2022

Cancers

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Carcinogenesis is a multistep process that consists of the transformation of healthy cells into cancer cells. Such an alteration goes through various stages and is closely linked to random mutations of genes that have a key role in the neoplastic phenotype. During carcinogenesis, cancer cells acquire and exhibit several characteristics including sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, and expressing an immune phenotype, which allow them to evade recognition and destruction through cognate immune cells. In addition, cancer cells may acquire the ability to reprogram their metabolism in order to further promote growth, survival, and energy production. This phenomenon, termed metabolic reprogramming, is typical of all solid tumors, including squamous carcinomas of the head and neck (SCCHN). In this review, we analyze the genetic and biological mechanisms underlying metabolic reprogramming of SCCHN, focusing on potential therapeutic strategies that are able to counteract it.

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New Immunometabolic Strategy Based on Cell Type-Specific Metabolic Reprogramming in the Tumor Immune Microenvironment

Cited by 21 publications

References 167 publications

Identification of cuproptosis-related subtypes, cuproptosis-related gene prognostic index in hepatocellular carcinoma

Identification of cuproptosis-related subtypes, cuproptosis-related gene prognostic index in hepatocellular carcinoma

Single Cell Analysis of Gastric Cancer Reveals Non-Defined Telomere Maintenance Mechanism

Cancer Cell Metabolism Reprogramming and Its Potential Implications on Therapy in Squamous Cell Carcinoma of the Head and Neck: A Review

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