Serum very long-chain fatty acid-containing lipids predict response to immune checkpoint inhibitors in urological cancers

Möck, Andreas; Zschäbitz, Stefanie; Kirsten, Romy; Scheffler, Matthias; Wolf, Barbara; Herold‐Mende, Christel; Kramer, Rebecca K.; Busch, Elena; Jenzer, Maximilian; Jäger, Dirk; Grüllich, Carsten

doi:10.1007/s00262-019-02428-3

Cited by 24 publications

(27 citation statements)

References 30 publications

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“…Accumulating evidence has demonstrated that dysregulation of lipid metabolism contributes to the progression of various metabolic diseases, including cancers, and targeting the pathways involved in lipid metabolism has become a novel anticancer strategy. Therefore, we explored the possible pathways that regulate lipid metabolism within the context of NTRK3 mutation and found that pathways related to cholesterol biosynthetic process and very long-chain fatty acid biosynthetic process, both of which are associated with increased antitumor immunity, were significantly upregulated in the NTRK3-MT group (Mock et al, 2019;Munir et al, 2019). Similarly, the pathways ATF6 (ATF6-alpha) activates chaperones, GPCR ligand binding and RHO GTPases activate NADPH oxidases, which affect pathways promoting tumorigenesis, were downregulated in the NTRK3-MT group (Bonner and Arbiser, 2012;O'Hayre et al, 2014;Lavoie and Garrett, 2018).…”

Section: Discussionmentioning

confidence: 99%

Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors

Niu¹,

Lin²,

Luo³

et al. 2020

Front. Pharmacol.

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Background: Immune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.

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Section: Discussionmentioning

confidence: 99%

Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors

Niu¹,

Lin²,

Luo³

et al. 2020

Front. Pharmacol.

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“…Suppressing tumor immune surveillance may lead to the exhaustion or inactivation of pro-inflammatory immune cells and may, subsequently, promote tumor growth and metastasis. Myeloid-derived suppressor cells (MDSC) and immunosuppressive type II (M2) tumor-associated macrophages (TAMs) are fueled by the ß-oxidation of lipids, rather than glycolysis, within the TME [ 42 ]. Recent studies have shown that the phenotype of M2-like TAMs is controlled by intracellular long-chain fatty acid (LCFA) homeostasis, specifically unsaturated fatty acids like oleate [ 43 ].…”

Section: Lipid Metabolism Impacts Immune Activation Against Tumor mentioning

confidence: 99%

“…The major clinical advantages of immune checkpoint inhibitors have generated considerable interest in discovering biomarkers that predict the response to treatment [ 88 ]. Recent studies propose serum concentrations of very long chain fatty acids (VLCFA) as a way to identify the response to immune checkpoint inhibitors in urological cancer [ 42 ]. The rationale for this biomarker is motivated by the finding that lower serum VLCFA levels are associated with highly immunosuppressive TME with a high-VLCFA consumption rate.…”

Section: Lipids As Biomarkers Of Immune Response To Cancermentioning

confidence: 99%

Lipidomic-Based Advances in Diagnosis and Modulation of Immune Response to Cancer

Balgoma

Montero

2020

Metabolites

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While immunotherapies for diverse types of cancer are effective in many cases, relapse is still a lingering problem. Like tumor cells, activated immune cells have an anabolic metabolic profile, relying on glycolysis and the increased uptake and synthesis of fatty acids. In contrast, immature antigen-presenting cells, as well as anergic and exhausted T-cells have a catabolic metabolic profile that uses oxidative phosphorylation to provide energy for cellular processes. One goal for enhancing current immunotherapies is to identify metabolic pathways supporting the immune response to tumor antigens. A robust cell expansion and an active modulation via immune checkpoints and cytokine release are required for effective immunity. Lipids, as one of the main components of the cell membrane, are the key regulators of cell signaling and proliferation. Therefore, lipid metabolism reprogramming may impact proliferation and generate dysfunctional immune cells promoting tumor growth. Based on lipid-driven signatures, the discrimination between responsiveness and tolerance to tumor cells will support the development of accurate biomarkers and the identification of potential therapeutic targets. These findings may improve existing immunotherapies and ultimately prevent immune escape in patients for whom existing treatments have failed.

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“…This allows to draw conclusions on individual metabolites, on the current metabolic phenotype and to detect potential deficiencies. For example, certain metabolic constellations can reflect a patient’s immune status (immunosuppressive vs. immunoprotective milieu) or serve as prognostic markers in oncology or cardiovascular diseases [ 3 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Perioperative changes in the plasma metabolome of patients receiving general anesthesia for pancreatic cancer surgery

et al. 2021

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Background: Modern anesthesia strives to offer personalized concepts to meet the patient's individual needs in sight of clinical outcome. Still, little is known about the impact of anesthesia on the plasma metabolome, although many metabolites have been shown to modulate the function of various immune cells, making it particularly interesting in the context of oncological surgery. In this study longitudinal dynamics in the plasma metabolome during general anesthesia in patients undergoing pancreatic surgery were analyzed.Materials and Methods: Prospective, observational study with 10 patients diagnosed with pancreatic (pre-) malignancy and subjected to elective resection surgery under general anesthesia. Plasma metabolites (n = 630) were quantified at eight consecutive perioperative timepoints using mass spectrometry-based targeted metabolomics.Results: 39 metabolites significantly changed during the perioperative period. Tryptophan concentrations decreased by 45% with the maximum decrease after anesthesia induction (p = 6.24E-07), while taurine synthesis increased (p = 1.46E-04). Triacylglycerides and lysophosphatidylcholines were significantly reduced with increased liberation of free monounsaturated fatty acids (p = 0.03). Carnitine levels decreased significantly (p = 9.30E-04).Conclusions: The major finding of this study was perioperative tryptophan depletion and increased taurine synthesis. Both are essential for immune cell function and are therefore of significant interest for perioperative management. Further studies are needed to identify influencing anesthetic factors.

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Serum very long-chain fatty acid-containing lipids predict response to immune checkpoint inhibitors in urological cancers

Cited by 24 publications

References 30 publications

Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors

Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors

Lipidomic-Based Advances in Diagnosis and Modulation of Immune Response to Cancer

Perioperative changes in the plasma metabolome of patients receiving general anesthesia for pancreatic cancer surgery

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