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Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma
Glutamine metabolism is critical both for the proliferation of cancer cells and the activation of CD8T cells to kill cancer cells. We aim to explore the relationship between the glutamine metabolism of CD8T cells and cancer cells and tumor immunity in the tumor microenvironment. In a TCGA cohort, we...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739589/ https://www.ncbi.nlm.nih.gov/pubmed/36497182 http://dx.doi.org/10.3390/cells11233924 |
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author | Chen, Jianfei Wang, Rui Liu, Zhongliang Fan, Jun Liu, Shenglu Tan, Shunde Li, Xinkai Li, Bo Yang, Xiaoli |
author_facet | Chen, Jianfei Wang, Rui Liu, Zhongliang Fan, Jun Liu, Shenglu Tan, Shunde Li, Xinkai Li, Bo Yang, Xiaoli |
author_sort | Chen, Jianfei |
collection | PubMed |
description | Glutamine metabolism is critical both for the proliferation of cancer cells and the activation of CD8T cells to kill cancer cells. We aim to explore the relationship between the glutamine metabolism of CD8T cells and cancer cells and tumor immunity in the tumor microenvironment. In a TCGA cohort, we found that patients with high scores of glutamine-metabolism-related genes showed poor prognoses, and that a high score of glutamine-metabolism-related genes was an independent risk factor for HCC patients. In single-cell RNA-seq data, we found that, in some patients, the glutamine metabolism gene scores of tumor cells were significantly higher than those of CD8T cells, while decreased ratios of CD8-Tef-GZMA and suppressed tumor-killing activity of CD8-Tef-APOC2 were observed. A further genetic dynamics pseudotime analysis suggested that immune remodeling of these two subpopulations was accompanied by metabolic reprogramming. CD8-Tef-APOC2 in the dominant group tended to metabolize exogenous lipids, while the metabolic program of CD8-Tef-GZMA in the nondominant group was characterized by amino acid and endogenous lipid synthesis. In addition, we found that the glutamine metabolism inhibitor JHU083 promoted the proliferation of CD8T cells and improved the efficacy of PD-1 blockers. We proposed a new tool to quantify the glutamine partitioning between tumor cells and CD8T cells, through which the unique immune microenvironment could be identified at the transcriptome level. Furthermore, the simultaneous destruction of the glutamine metabolism in tumor cells and CD8T cells facilitated the enrichment of tumor-infiltrating CD8T cells and enhanced the efficacy of immunotherapy. |
format | Online Article Text |
id | pubmed-9739589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97395892022-12-11 Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma Chen, Jianfei Wang, Rui Liu, Zhongliang Fan, Jun Liu, Shenglu Tan, Shunde Li, Xinkai Li, Bo Yang, Xiaoli Cells Article Glutamine metabolism is critical both for the proliferation of cancer cells and the activation of CD8T cells to kill cancer cells. We aim to explore the relationship between the glutamine metabolism of CD8T cells and cancer cells and tumor immunity in the tumor microenvironment. In a TCGA cohort, we found that patients with high scores of glutamine-metabolism-related genes showed poor prognoses, and that a high score of glutamine-metabolism-related genes was an independent risk factor for HCC patients. In single-cell RNA-seq data, we found that, in some patients, the glutamine metabolism gene scores of tumor cells were significantly higher than those of CD8T cells, while decreased ratios of CD8-Tef-GZMA and suppressed tumor-killing activity of CD8-Tef-APOC2 were observed. A further genetic dynamics pseudotime analysis suggested that immune remodeling of these two subpopulations was accompanied by metabolic reprogramming. CD8-Tef-APOC2 in the dominant group tended to metabolize exogenous lipids, while the metabolic program of CD8-Tef-GZMA in the nondominant group was characterized by amino acid and endogenous lipid synthesis. In addition, we found that the glutamine metabolism inhibitor JHU083 promoted the proliferation of CD8T cells and improved the efficacy of PD-1 blockers. We proposed a new tool to quantify the glutamine partitioning between tumor cells and CD8T cells, through which the unique immune microenvironment could be identified at the transcriptome level. Furthermore, the simultaneous destruction of the glutamine metabolism in tumor cells and CD8T cells facilitated the enrichment of tumor-infiltrating CD8T cells and enhanced the efficacy of immunotherapy. MDPI 2022-12-04 /pmc/articles/PMC9739589/ /pubmed/36497182 http://dx.doi.org/10.3390/cells11233924 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Jianfei Wang, Rui Liu, Zhongliang Fan, Jun Liu, Shenglu Tan, Shunde Li, Xinkai Li, Bo Yang, Xiaoli Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma |
title | Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma |
title_full | Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma |
title_fullStr | Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma |
title_full_unstemmed | Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma |
title_short | Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma |
title_sort | unbalanced glutamine partitioning between cd8t cells and cancer cells accompanied by immune cell dysfunction in hepatocellular carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739589/ https://www.ncbi.nlm.nih.gov/pubmed/36497182 http://dx.doi.org/10.3390/cells11233924 |
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