Glutaminase inhibition impairs CD8 T cell activation in STK11-/Lkb1-deficient lung cancer

Best, Sarah A.; Gubser, Patrick; Sethumadhavan, Shalini; Kersbergen, Ariena; Abril, Yashira L. Negrón; Goldford, Joshua E.; Sellers, Katherine; Abeysekera, Waruni; Garnham, Alexandra L.; McDonald, Jackson A.; Weeden, Clare E.; Anderson, Dovile; Pirman, David; Roddy, Thomas P.; Creek, Darren J.; Kallies, Axel; Kingsbury, Gillian A.; Sutherland, Kate D.

doi:10.1016/j.cmet.2022.04.003

Cited by 73 publications

(65 citation statements)

References 81 publications

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“…With the progression of biological immune system and tumor immune contexture, immunotherapy has been widely adapted in clinical patients (Best et al, 2022;Di Luccia and Colonna, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…With the progression of biological immune system and tumor immune contexture, immunotherapy has been widely adapted in clinical patients ( Best et al, 2022 ; Di Luccia and Colonna, 2022 ). However, the efficiency of immunotherapy differs greatly in individuals with divergent tumor immune contexture ( Guillerey et al, 2016 ; Ciardiello et al, 2022 ; Liu et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive analysis of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in colorectal cancer

Zhu

Zhao²,

Li³

et al. 2022

Front. Genet.

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Background: Cuproptosis is a novel form of cell death discovered in recent. A great quantity of researches has confirmed the close relationships and crucial roles between long non-coding RNAs (lncRNAs) with the progression of colorectal cancer (CRC). However, the relationship between cuproptosis and lncRNAs remains unclear in CRC.Methods: 1,111 co-expressed lncRNAs with 16 cuproptosis regulators were retrieved from CRC samples of The Cancer Genome Atlas (TCGA) database. Through univariate Cox and least absolute shrinkage and selection operator regression analysis, a prognosis model was constructed with 15 lncRNAs. The Kaplan-Meier, receiver operating characteristic curve, C-index and principal component analysis identified the prognostic power. Furthermore, a cuproptosis-related cluster was generated based on the 15 lncRNAs by unsupervised methods. The correlations between the cuproptosis-related signatures with immune cell infiltration and anti-tumor therapy were explored by multiple algorithms.Results: A risk score and nomogram with great prediction ability were constructed for CRC prognosis evaluation. The immune activate pathways, immune infiltration cells, immune functions, immune score and immune activation genes were remarkably enriched in the high risk group. The cuproptosis-related cluster was generated, of which the cluster 2 showed longer overall survival. The immune cell infiltration analysis indicated the similar results of cluster 2 with the high risk group, implying a significant marker for “hot tumor.” The cluster 2 also presented high expression of immune checkpoint molecules, MSI-H status and higher susceptibility to multiple immunotherapy drugs.Conclusion: We appraised a novel cuproptosis-related prognosis model and molecular signature associated with prognosis, immune infiltration and immunotherapy. The identification of cuproptosis-related lncRNAs improved our understanding of immune infiltration and provided a significant marker for prognosis and immunotherapy in CRC.

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“…With the progression of biological immune system and tumor immune contexture, immunotherapy has been widely adapted in clinical patients (Best et al, 2022;Di Luccia and Colonna, 2022).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in colorectal cancer

Zhu

Zhao²,

Li³

et al. 2022

Front. Genet.

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“…Therefore, regulation of nutrient metabolism can impact the function of T cells. Inhibiting glutaminase, an amidohydrolase enzyme that can generate glutamate from glutamine, can also suppress CD8 + T cell activation induced by anti-PD-1 immunotherapy[ 23 ].…”

Section: To the Editormentioning

confidence: 99%

Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma

Zhang¹,

Liu²,

Yang³

2022

WJGO

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the third leading cause of cancer-related death worldwide. Factors including carcinogens, infection of hepatitis viruses, alcohol abuse, and metabolic disorders such as non-alcoholic fatty liver disease mainly contribute to HCC initiation and progression. Immunotherapy is one of the most powerful tools for unresectable HCC treatment in patients. CD8 + T cells are a major immune component in the tumor microenvironment with cytotoxic effects against cancer cells. However, these CD8 + T cells commonly display an exhaustion phenotype with high expression of programmed cell death protein 1, T-cell immunoglobulin and mucin-domain containing-3, and/or lymphocyte-activation gene 3, producing low levels of perforin (PRF1) and granzyme B (GZMB), as well as anti-tumor cytokines, such as interferon gamma and tumor necrosis factor alpha. In the referenced study, the authors also showed that deprivation of glutamine decreased the antitumor function of CD8 + T cells, as well as the production of PRF1 and GZMB. However, the role of each amino acid in T cell function and exhaustion may depend on tumor type and tumor microenvironment, including the source of other nutrients. Overall, amino acids or other nutrient metabolites in the tumor microenvironment play a pivotal role in both tumor growth and immune response.

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“…Glutamine can also act as a nitrogen donor for the synthesis of purine and pyrimidine nucleotides, amino acids, and other metabolites. Finally, glutamine catabolism results in the production of lactate, alanine, and ammonia, thus maintaining non-essential amino acid pools [ 12 , 13 , 14 , 15 , 16 ]. An increased production of NADPH is essential for the biosynthesis of fatty acids and serves as the ultimate donor of reductive power for detoxifying the cell from the enormous amount of reactive oxygen species (ROS) that accumulate as a result of the high proliferation rate.…”

Section: Metabolic Shift In Cancer Cellsmentioning

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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Glutaminase inhibition impairs CD8 T cell activation in STK11-/Lkb1-deficient lung cancer

Cited by 73 publications

References 81 publications

Comprehensive analysis of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in colorectal cancer

Comprehensive analysis of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in colorectal cancer

Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma

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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