From tumor cell metabolism to tumor immune escape

Villalba, Martín; Rathore, Moeez Ghani; López-Royuela, Nuria; Krzywińska, Ewelina; Garaude, Johan; Allende-Vega, Nerea

doi:10.1016/j.biocel.2012.04.024

Cited by 88 publications

(94 citation statements)

References 83 publications

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“…Tumor immune escape plays an important role in the development and metastasis of tumors [35]. Multiple immunosuppressive mechanisms in the tumor microenvironment can impair the functions of tumor-infiltrating lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme catalyzing the initial and rate-limiting steps in the kynurenine pathway, which converts tryptophan into kynurenine. Upregulation of IDO1 decreases tryptophan levels and increases the accumulation of kynurenine and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence has shown that IDO1 is highly expressed in various cancer types and associated with poor prognosis of cancer patients. However, the results were inconsistent. Methods: We searched the Web of Science, PubMed, Embase and Cochrane library databases to identify studies evaluating the prognostic value of IDO1 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using fixed-effects/random-effects models. Results: This systematic review and meta-analysis included 2706 patients from 24 articles. The results indicated a shorter overall survival in patients with high expression of IDO1 (hazard ratio [HR] = 2.03, 95% confidence interval [CI]: 1.56-2.63). Furthermore, disease-free survival was worse in patients with high expression of IDO1 (HR = 2.47, 95% CI: 1.46-4.20). Additionally, the pooled odds ratios (ORs) showed that increased IDO1 was significantly associated with tumor differentiation (OR = 1.81, 95% CI: 1.05-3.12), distant metastasis (OR = 1.45, 95% CI: 1.02-2.06), and poor clinical stage (OR = 1.89, 95% CI: 1.13-3.17). However, no significant correlation was observed of increased IDO1 expression with age, sex, lymph node metastasis, and tumor size. Conclusion: High expression of IDO1 is associated with poor clinical outcomes. IDO1 could serve as a biomarker of prognosis and a potential predictive factor of clinicopathology in various cancers. Further studies should be performed to verify the clinical utility of IDO1 in human solid tumors.

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Section: Discussionmentioning

confidence: 99%

The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis

Chen

et al. 2018

Cell Physiol Biochem

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“…To induce their lethal effects and maintain survival, tumour cells alter their metabolism to ensure survival, evade host immune attack, and proliferate [7]. This clever strategy of tumour cells was exposed by Otto Warburg in the 1920s when he proved that, in spite of the presence of abundant oxygen, tumour cells metabolise glucose via glycolysis to produce lactate.…”

Section: Tumour Cell Metabolismmentioning

confidence: 99%

Cancer stem cell metabolism: a potential target for cancer therapy

2016

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Cancer Stem cells (CSCs) are a unipotent cell population present within the tumour cell mass. CSCs are known to be highly chemo-resistant, and in recent years, they have gained intense interest as key tumour initiating cells that may also play an integral role in tumour recurrence following chemotherapy. Cancer cells have the ability to alter their metabolism in order to fulfil bio-energetic and biosynthetic requirements. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilisation. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to dysregulation in glucose metabolism, fatty acid synthesis, and glutaminolysis. To propagate their lethal effects and maintain survival, tumour cells alter their metabolic requirements to ensure optimal nutrient use for their survival, evasion from host immune attack, and proliferation. It is now evident that cancer cells metabolise glutamine to grow rapidly because it provides the metabolic stimulus for required energy and precursors for synthesis of proteins, lipids, and nucleic acids. It can also regulate the activities of some of the signalling pathways that control the proliferation of cancer cells.This review describes the key metabolic pathways required by CSCs to maintain a survival advantage and highlights how a combined approach of targeting cellular metabolism in conjunction with the use of chemotherapeutic drugs may provide a promising strategy to overcome therapeutic resistance and therefore aid in cancer therapy.

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“…The differential regulation of tumor metabolism and the relative abundance of some tumor-derived metabolites have also been shown to condition the tumor microenvironment, with particular emphasis on immune cell components (5). For example, metabolic products like pyruvic acid and lactic acid induce hypoxiaindependent stabilization of HIF-1α in tumor-associated macrophages (6).…”

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confidence: 99%

24-Hydroxycholesterol participates in pancreatic neuroendocrine tumor development

Soncini

Corna

Moresco

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cells in the tumor microenvironment may be reprogrammed by tumor-derived metabolites. Cholesterol-oxidized products, namely oxysterols, have been shown to favor tumor growth directly by promoting tumor cell growth and indirectly by dampening antitumor immune responses. However, the cellular and molecular mechanisms governing oxysterol generation within tumor microenvironments remain elusive. We recently showed that tumorderived oxysterols recruit neutrophils endowed with protumoral activities, such as neoangiogenesis. Here, we show that hypoxia inducible factor-1a (HIF-1α) controls the overexpression of the enzyme Cyp46a1, which generates the oxysterol 24-hydroxycholesterol (24S-HC) in a pancreatic neuroendocrine tumor (pNET) model commonly used to study neoangiogenesis. The activation of the HIF-1α-24S-HC axis ultimately leads to the induction of the angiogenic switch through the positioning of proangiogenic neutrophils in proximity to Cyp46a1 + islets. Pharmacologic blockade or genetic inactivation of oxysterols controls pNET tumorigenesis by dampening the 24S-HC-neutrophil axis. Finally, we show that in some human pNET samples Cyp46a1 transcripts are overexpressed, which correlate with the HIF-1α target VEGF and with tumor diameter. This study reveals a layer in the angiogenic switch of pNETs and identifies a therapeutic target for pNET patients.oxysterols | HIF-1α | pancreatic neuroendocrine tumors | angiogenic switch | neutrophils R ecent studies have highlighted the diversity of metabolic pathways altered between normal and tumor cells (1, 2). Activation of specific metabolic pathways within tumors is believed to derive from an intricate connection among intrinsic and extrinsic factors, such as oncogenic signaling, stromal-derived molecules, and hypoxia (3). Tumor hypoxia and hypoxia inducible factor-1a (HIF-1α) activation have been linked to increased glucose metabolism and cancer progression in a number of tumor types (4). Whether HIF-1α signaling regulates other metabolic products in tumor cells or during tumorigenesis remains only partially understood.The differential regulation of tumor metabolism and the relative abundance of some tumor-derived metabolites have also been shown to condition the tumor microenvironment, with particular emphasis on immune cell components (5). For example, metabolic products like pyruvic acid and lactic acid induce hypoxiaindependent stabilization of HIF-1α in tumor-associated macrophages (6). These products, especially lactic acid, are products of the so-called Warburg effect (aerobic glycolysis) (7) and mainly require the enzymatic activity of the pyruvate kinase M2 (PKM2), an isoform expressed by tumor cells and associated with the production of high amounts of pyruvate and lactate (8). More recently cholesterol metabolism, oxysterols, and liver X receptors (LXRs) have been shown to be important players in tumor metabolism (9, 10), due to their dual involvement in tumor and immune cell biology (11-13). This dual involvement makes the LXR/oxysterol axis an attractive ta...

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From tumor cell metabolism to tumor immune escape

Cited by 88 publications

References 83 publications

The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis

The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis

Cancer stem cell metabolism: a potential target for cancer therapy

24-Hydroxycholesterol participates in pancreatic neuroendocrine tumor development

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