scholarly journals Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shi-yi Wu ◽  
Pan Liao ◽  
Lu-yu Yan ◽  
Qian-yi Zhao ◽  
Zhao-yu Xie ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Vital Role ◽  
Prediction Performance ◽  
Liver Carcinoma ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Immune Infiltration ◽  
Prognosis Prediction ◽  
Prognostic Prediction

Abstract Background MKI67 plays a vital role in the tumour microenvironment (TME) and congenital immunity. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatocellular liver carcinoma (LIHC). Methods Oncomine, GEPIA2, and HPA were adopted to analyse MKI67 levels in different types of cancers. The prognostic prediction performance of MKI67 was evaluated through the TCGA portal, GEPIA2, LOGpc, and Kaplan–Meier Plotter databases. The associations of MKI67 with related gene marker sets and immune infiltration were inspected through TISIDB, GEPIA2, and TIMER. We chose MKI67 to analyse biological processes (BPs) and KEGG pathways related to the coexpressed genes. Furthermore, the gene–miRNA interaction network for MKI67 in liver cancer was also examined based on the miRWalk database. Results MKI67 expression decreased in many cancers related to the dismal prognostic outcome of LIHC. We found that MKI67 significantly affected the prognosis of LIHC in terms of histology and grade. Increased MKI67 levels were directly proportional to the increased immune infiltration degrees of numerous immune cells and functional T cells, such as exhausted T cells. In addition, several critical genes related to exhausted T cells, including TIM-3, TIGIT, PD-1, LAG3, and CXCL13, were strongly related to MKI67. Further analyses showed that MKI67 was associated with adaptive immunity, cell adhesion molecules (CAMs), and chemokine/immune response signal transduction pathways. Conclusion MKI67 acts as a prognostic prediction biomarker in several cancers, particularly LIHC. Upregulation of MKI67 elevates the degree of immune infiltration of many immune cell subtypes, including functional T cells, CD4+ T cells, and CD8+ T cells. Furthermore, MKI67 shows a close correlation with T cell exhaustion, which plays a vital role in promoting T cell exhaustion within LIHC. Detection of the MKI67 level contributes to prognosis prediction and MKI67 modulation within exhausted T cells, thus providing a new method to optimize the efficacy of anti-LIHC immunotherapy.

scholarly journals CXCL13 Correlates with Prognosis, Immune Infiltration, and T Cell Exhaustion in Ovarian Cancer

2021 ◽  
Author(s):  
Hailing Duan ◽  
Ying Lv ◽  
Pan Liao ◽  
Yiming Wang ◽  
Zhifang Zheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Cell Adhesion ◽  
T Cell ◽  
Immune Cells ◽  
Gene Marker ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Immune Infiltration ◽  
Prognosis Prediction

Abstract Background: CXCL13 is an important chemotactic factor closely related to the biology of cancer cells. The presence work focused on exploring the significance of CXCL13 in prognosis prediction and analyzing the associations of CXCL13 with T cell function and immune infiltration in various cancers, especially ovarian cancer (OV).Purpose: CXCL13 is associated with prognosis, immune infiltration, and T cell failure of ovarian cancer.Methods: The Oncomine, GEPIA2 and HPA databases were utilized for analyzing CXCL13 levels within diverse cancers. The significance of CXCL13 in prognosis prediction was explored through Kaplan-Meier Plotter, TCGAportal, and GEPIA2. Meanwhile, the associations of CXCL13 with clinical stage, gene marker sets, and immune infiltration were examined through TISIDB, GEPIA2, and TIMER databases. Besides, CXCL13 was screened to analyze the biological processes (BPs) and KEGGs enriched by co-expression genes. The miRWalk database was employed for analyzing the gene-miRNA interaction network of CXCL13 within OV.Results: CXCL13 expression decreased in many cancers, which predicted the dismal survival of OV. CXCL13 upregulation was in direct proportion to the increased immune infiltration degrees of many functional T cells (like exhausted T cells) and immune cells. Additionally, some critical genes of exhausted T cells, such as TIM-3, PD-1, LAG3, TIGIT, GZMB, and CXCL13, were closely associated with CXCL13. Moreover, CXCL13 was related to immune response regulatory signaling pathway, leukocyte cell-cell adhesion, cell adhesion molecules (CAMs), and hematopoietic cell lineage. Conclusion: CXCL13 can serve as a biomarker to predict cancer prognosis, particularly OV. CXCL13 upregulation remarkably elevates the immune infiltration degrees of numerous immune cells, like mast cells, CD8+ T cells, natural killer (NK) cells, and dendritic cells (DCs). Furthermore, CXCL13 is suggested to be closely related to exhausted T cells, which may be used as a candidate regulating factor for T cell exhaustion within OV. Detecting CXCL13 levels contributes to prognosis prediction and CXCL13 regulation within exhausted T cells, which provides a new approach to maximizing the anti-OV efficacy of immunotherapy.

scholarly journals PLAC8 Correlates with Prognosis, Immune Infiltration, and T Cell Exhaustion in Breast Cancer

2021 ◽  
Author(s):  
Pan Liao ◽  
Ying Wang ◽  
Lixia Sun ◽  
Hongpeng Yue
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Prognostic Significance ◽  
Her2 Status ◽  
Gene Marker ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Immune Infiltration

Abstract Background: Lysosomal protein placenta-specific 8 (PLAC8) with abundant cysteine, also referred to as onzin, participates in numerous cancers, and its effect is greatly determined by the cellular and tumor microenvironment (TME). Ourstudy focused on investigating the prognostic significance of PLAC8 and examined the association between PLAC8, immune infiltration, and T cells function in multiple malignancies comprehensively, particularly in breast cancer (BRCA).Methods: PLAC8 expression in various malignancies was analyzed using TIMER. PrognoScan, Kaplan-Meier Plotter, and GEPIA2 were utilized to explore the significance of PLAC8 in prognostic prediction. Moreover, PLAC8 functions were systematically analyzed through cancerSEA. Additionally, TISIDB, TIMER, and GEPIA2 were also employed for analyzing the associations among PLAC8, immune infiltration, related gene marker sets, and clinical stages. Finally, PLAC8 and its co-expressed genes biological process and KEGG were analyzed. Results: PLAC8 expression decreased in most malignancies and was related to poor prognosis in BRCA. PLAC8 significantly affected the survival of BRCA with ER status – array, PR status – IHC, HER2 status – array, Intrinsic subtype, Grade, and Pietenpol subtype. Increased PLAC8 expression positively correlated with the increased immune infiltration levels within immune cells and many functional T cells (such as exhausted T cells). In BRCA cells, PLAC8 functional phenotypesshowed a negative correlation with invasion, metastasis, apoptosis, DNA damage, and DNA repair. Besides, PD-1, TIM-3, TIGIT, LAG3, and GZMB, critical genes of exhausted T cells, interacted with PLAC8. Further analysis indicated that PLAC8 was related to T cell activation, proliferation and adhesion of leukocytes,adaptive immune response, cell adhesion molecules (CAMs), cytotoxicity-mediated by natural killer cells, and the NF-kappa B signal transduction pathway.Conclusion:PLAC8 is a prognostic indicator in pan-cancers, especially BRCA. Elevated PLAC8 level could significantly enhance immune infiltration in CD4+ T cells, CD8+ T cells, and functional T cells. Additionally, PLAC8 was tightly associatedwith T cell exhaustion which possibly enhances the latterwithin BRCA. PLAC8 expression determination might help in prognosis, and modulation of PLAC8level within exhausted T cells, a novel approach for optimizing the therapeutic effect of immunotherapy on BRCA cases.

scholarly journals AGTRAP Is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Shanshan Liu ◽  
Wei Zhao ◽  
Xuemei Li ◽  
La Zhang ◽  
Yu Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Normal Liver ◽  
Mrna Levels ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Immune Infiltration ◽  
Protein Levels ◽  
Liver Tissues

BackgroundRecently, it has been reported that angiotensin II receptor-associated protein (AGTRAP) plays a substantial role in tumor progression. Nevertheless, the possible role of AGTRAP in hepatocellular carcinoma (HCC) remains unrecognized.MethodsThe metabolic gene rapid visualizer, Cancer Cell Line Encyclopedia, Human Protein Atlas, and Hepatocellular Carcinoma Database were used to analyze the expression of AGTRAP in HCC tissues and normal liver tissues or adjacent tissues. Kaplan-Meier plotter and UALCAN analysis were used to assess the prognostic and diagnostic value of AGTRAP. LinkedOmics and cBioPortal were used to explore the genes co-expressed with AGTRAP in HCC. To further understand the potential mechanism of AGTRAP in HCC, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathway analyses were performed using R software, the protein-protein interaction (PPI) network was established using the STRING database, and the immune infiltration and T-cell exhaustion related to AGTRAP were explored via Timer and GEPIA. In addition, immunohistochemistry was used to detect the expression of AGTRAP protein in HCC tissues and paired adjacent tissues from clinical specimens.ResultsThis study found that the mRNA and protein levels of AGTRAP in HCC tissues were higher than those in normal liver tissues and adjacent tissues, and higher mRNA levels of AGTRAP were associated with higher histological grade and a poor overall survival in HCC patients. The area under the receiver operating characteristic curve (AUC) of AGTRAP was 0.856, suggesting that it could be a diagnostic marker for HCC. Moreover, the alteration rate of AGTRAP in HCC was 8%, and AGTRAP was involved in HCC probably through the NF-κB and MAPK signaling pathways. Furthermore, AGTRAP was positively correlated with the infiltration of CD8+ T cells, CD4+ T cells, B cells, macrophages, dendritic cells, and neutrophils, and the levels of AGTRAP were significantly correlated with T-cell exhaustion biomarkers. The immunohistochemistry results confirmed that the protein levels of AGTRAP were consistently higher in HCC tissues than in paired adjacent tissues.ConclusionThe clinical value of AGTRAP and its correlation with immune infiltration in HCC was effectively identified in clinical data from multiple recognized databases. These findings indicate that AGTRAP could serve as a potential biomarker in the treatment of HCC, thereby informing its prognosis, diagnosis, and even immunotherapy.

scholarly journals Tim-3 adaptor protein Bat3 is a molecular checkpoint of T cell terminal differentiation and exhaustion

2021 ◽  
Vol 7 (18) ◽  
pp. eabd2710
Author(s):  
Chen Zhu ◽  
Karen O. Dixon ◽  
Kathleen Newcomer ◽  
Guangxiang Gu ◽  
Sheng Xiao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adaptor Protein ◽  
Transcriptional Analysis ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Cell Dysfunction ◽  
Autoreactive T Cell ◽  
Autoimmune Conditions ◽  
T Cell Dysfunction

T cell exhaustion has been associated with poor prognosis in persistent viral infection and cancer. Conversely, in the context of autoimmunity, T cell exhaustion has been favorably correlated with long-term clinical outcome. Understanding the development of exhaustion in autoimmune settings may provide underlying principles that can be exploited to quell autoreactive T cells. Here, we demonstrate that the adaptor molecule Bat3 acts as a molecular checkpoint of T cell exhaustion, with deficiency of Bat3 promoting a profound exhaustion phenotype, suppressing autoreactive T cell–mediated neuroinflammation. Mechanistically, Bat3 acts as a critical mTORC2 inhibitor to suppress Akt function. As a result, Bat3 deficiency leads to increased Akt activity and FoxO1 phosphorylation, indirectly promoting Prdm1 expression. Transcriptional analysis of Bat3−/− T cells revealed up-regulation of dysfunction-associated genes, concomitant with down-regulation of genes associated with T cell effector function, suggesting that absence of Bat3 can trigger T cell dysfunction even under highly proinflammatory autoimmune conditions.

scholarly journals Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254243
Author(s):  
Meritxell Llorens-Revull ◽  
Maria Isabel Costafreda ◽  
Angie Rico ◽  
Mercedes Guerrero-Murillo ◽  
Maria Eugenia Soria ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Hepatitis C ◽  
T Cell ◽  
Cd8 T Cells ◽  
Viral Clearance ◽  
Cd4 T Cell ◽  
Care Hospital ◽  
T Cell Exhaustion ◽  
Cell Exhaustion

Background & aims HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV. Methods We analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-Ɣ ELISPOT, intracellular cytokine staining (IL-2 and IFN-Ɣ) and CFSE-based proliferation assays. Results We observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-Ɣ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies. Conclusions Our results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA’s therapies.

scholarly journals Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Weiqin Jiang ◽  
Yinjun He ◽  
Wenguang He ◽  
Guosheng Wu ◽  
Xile Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Burden ◽  
Effector Function ◽  
T Cell Exhaustion ◽  
Immune Microenvironment ◽  
Cell Exhaustion ◽  
Combination Strategies ◽  
Cell Pool ◽  
Tumor Immune Microenvironment

Tumor-specific CD8+T cells are exposed to persistent antigenic stimulation which induces a dysfunctional state called “exhaustion.” Though functioning to limit damage caused by immune response, T cell exhaustion leads to attenuated effector function whereby cytotoxic CD8+T cells fail to control tumor progression in the late stage. This pathway is a dynamic process from activation to “progenitor exhaustion” through to “terminally exhaustion” with distinct properties. With the rapid development of immunotherapy via enhancing T cell function, new studies are dissecting the mechanisms and identifying specific biomarkers of dynamic differentiation during the process of exhaustion. Further, although immune checkpoint inhibitors (ICIs) have achieved great success in clinical practice, most patients still show limited efficacy to ICIs. The expansion and differentiation of progenitor exhausted T cells explained the success of ICIs while the depletion of the progenitor T cell pool and the transient effector function of terminally exhausted T cells accounted for the failure of immune monotherapy in the context of exorbitant tumor burden. Thus, combination strategies are urgent to be utilized based on the reduction of tumor burden or the expansion of the progenitor T cell pool. In this review, we aim to introduce the concept of homeostasis of the activated and exhausted status of CD8+T cells in the tumor immune microenvironment, and present recent findings on dynamic differentiation process during T cell exhaustion and the implications for combination strategies in immune therapy.

scholarly journals 644 Tumor-mediated suppressive signaling and hypoxia supports altered chromatin landscapes that limit the transcriptional and functional potential of terminal T cell exhaustion

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A673-A673
Author(s):  
Rhodes Ford ◽  
Natalie Rittenhouse ◽  
Nicole Scharping ◽  
Paolo Vignali ◽  
Greg Delgoffe ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Histone Modifications ◽  
Cd8 T Cells ◽  
Tumor Hypoxia ◽  
T Cell Subsets ◽  
T Cell Exhaustion ◽  
Cell Exhaustion

BackgroundCD8+ T cells are a fundamental component of the anti-tumor response; however, tumor-infiltrating CD8+ T cells (TIL) are rendered dysfunctional by the tumor microenvironment. CD8+ TIL display an exhausted phenotype with decreased cytokine expression and increased expression of co-inhibitory receptors (IRs), such as PD-1 and Tim-3. The acquisition of IRs mark the progression of dysfunctional TIL from progenitors (PD-1Low) to terminally exhausted (PD-1+Tim-3+). How the chromatin landscape changes during this progression has not been described.MethodsUsing a low-input ChIP-based assay called Cleavage Under Targets and Release Using Nuclease (CUT&RUN), we have profiled the histone modifications at the chromatin of tumor-infiltrating CD8+ T cell subsets to better understand the relationship between the epigenome and the transcriptome as TIL progress towards terminal exhaustion.ResultsWe have identified two epigenetic characteristics unique to terminally exhausted cells. First, we have identified a unique set of genes, characterized by active histone modifications that do not have correlated gene expression. These regions are enriched for AP-1 transcription factor motifs, yet most AP-1 family factors are actively downregulated in terminally exhausted cells, suggesting signals that promote downregulation of AP-1 expression negatively impacts gene expression. We have shown that inducing expression of AP-1 factors with a 41BB agonist correlates with increased expression of these anticorrelated genes. We have also found a substantial increase in the number of genes that exhibit bivalent chromatin marks, defined by the presence of both active (H3K4me3) and repressive (H3K27me3) chromatin modifications that inhibit gene expression. These bivalent genes in terminally exhausted T cells are not associated with plasticity and represent aberrant hypermethylation in response to tumor hypoxia, which is necessary and sufficient to promote downregulation of bivalent genes.ConclusionsOur study defines for the first time the roles of costimulation and the tumor microenvironment in driving epigenetic features of terminally exhausted tumor-infiltrating T cells. These results suggest that terminally exhausted T cells have genes that are primed for expression, given the right signals and are the basis for future work that will elucidate that factors that drive progression towards terminal T cell exhaustion at the epigenetic level and identify novel therapeutic targets to restore effector function of tumor T cells and mediate tumor clearance.

scholarly journals VitaminD3 Regulates T Cell Immune Responses in Allergen and Rhinovirus Induced Asthma

2021 ◽  
Author(s):  
Susetta Finotto ◽  
Patricia Haag ◽  
Darja Andreev ◽  
Nina Li ◽  
Alexander Kiefer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Murine Model ◽  
Peripheral Blood ◽  
Serum Levels ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Asthmatic Children ◽  
Rhinovirus Infection

Abstract Background: Serum 25(OH)-Vitamin D3 (VitD3) deficiency during infancy has been associated with asthma. The potential therapeutic role of VitD3 given in the airways and its interference with the allergen and Rhinovirus was the objective of this study. Methods: In two cohorts of children with and without asthma, serum levels of the C-reactive protein (CRP) were correlated to Serum VitD3 and in peripheral blood T cell inhibitor marker Programmed cell death protein 1 (PD1) mRNA was analyzed. In a murine model, VitD3 was given intranasally in vivo and in vitro to lung cells with allergen and Rhinovirus. Results: In the cohorts of pre-school age children without (control) asthma, CRP and VitD3 levels inversely correlated. In preschool asthmatic children that did not receive VitD3 supplementation as infant had more episode of asthma exacerbation associated with high CRP serum level. In peripheral blood cells from control but not asthmatic children with higher serum levels of VitD3 had lower PD1 mRNA levels. In murine model, OVA intranasal challenge induced Innate Lymphoid Cells type 2 (ILC2)-associated markers and Eosinophils in BALF and VitD3 inhibited lung inflammation and ILC2 markers. Furthermore, VitD3 given intranasally, induced CD4+T cells and reduced PD1, T regulatory cells in the lung. Similarly, VitD3 had a suppressive role on CD4+PD1+ T cells involved in T cell exhaustion in the airways in the absence of ST2 after Rhinovirus infection. Conclusion: These data support an inhibitory role of VitD3 on T cell exhaustion after allergen and rhinovirus infection that is relevant for pediatric asthma.

scholarly journals Single-Cell Transcriptome Analysis Reveals RGS1 as a New Marker and Promoting Factor for T-Cell Exhaustion in Multiple Cancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunmeng Bai ◽  
Meiling Hu ◽  
Zixi Chen ◽  
Jinfen Wei ◽  
Hongli Du
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Poor Prognosis ◽  
Effector T Cells ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Cell Transcriptome ◽  
Cancer Tissues ◽  
Single Cell Transcriptome

T-cell exhaustion is one of the main reasons of tumor immune escape. Using single-cell transcriptome data of CD8+ T cells in multiple cancers, we identified different cell types, in which Pre_exhaust and exhausted T cells participated in negative regulation of immune system process. By analyzing the coexpression network patterns and differentially expressed genes of Pre_exhaust, exhausted, and effector T cells, we identified 35 genes related to T-cell exhaustion, whose high GSVA scores were associated with significantly poor prognosis in various cancers. In the differentially expressed genes, RGS1 showed the greatest fold change in Pre_exhaust and exhausted cells of three cancers compared with effector T cells, and high expression of RGS1 was also associated with poor prognosis in various cancers. Additionally, RGS1 protein was upregulated significantly in tumor tissues in the immunohistochemistry verification. Furthermore, RGS1 displayed positive correlation with the 35 genes, especially highly correlated with PDCD1, CTLA4, HAVCR2, and TNFRSF9 in CD8+ T cells and cancer tissues, indicating the important roles of RGS1 in CD8+ T-cell exhaustion. Considering the GTP-hydrolysis activity of RGS1 and significantly high mRNA and protein expression in cancer tissues, we speculated that RGS1 potentially mediate the T-cell retention to lead to the persistent antigen stimulation, resulting in T-cell exhaustion. In conclusion, our findings suggest that RGS1 is a new marker and promoting factor for CD8+ T-cell exhaustion and provide theoretical basis for research and immunotherapy of exhausted cells.

scholarly journals Metabolic Reprogramming and Intervention During T Cell Exhaustion

2021 ◽  
Author(s):  
Fei Li ◽  
Huiling Liu ◽  
Dan Zhang ◽  
Bingdong Zhu
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Cell Metabolism ◽  
T Cell Exhaustion ◽  
Naive T Cells ◽  
Cell Exhaustion ◽  
Naïve T Cells ◽  
T Cell Function ◽  
Prevention And Treatment

Recent studies have shown that T cell metabolism has become a key regulator of T cell function and even can determine T cell function at last. Naïve T cells use fatty acid oxidation (FAO) to meet their energetic demands. Effector T cells mainly rely on aerobic glycolysis to supply energy and synthesize intermediate products. Similar to naïve T cells, memory T cells primarily utilize FAO for energy. Exhausted T cells, which can be induced by continuous activation of T cells upon persistently chronic infections such as tuberculosis, mainly rely on glycolysis for energy. The prevention and treatment of T cell exhaustion is facing great challenges. Interfering T cell metabolism may achieve the goal of prevention and treatment of T cell exhaustion. In this review, we compiled the researches related to exhausted T cell metabolism and put forward the metabolic intervention strategies to reverse T cell exhaustion at different stages to achieve the purpose of preventing and treating T cell exhaustion.

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