TIM-3: An update on immunotherapy

Zhao, Li‐Zhen; Cheng, Shaoyun; Fan, Lin; Zhang, Bei; Xu, Shengwei

doi:10.1016/j.intimp.2021.107933

Cited by 105 publications

(88 citation statements)

References 84 publications

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“…CD209 has been reported to be correlated with M2 like macrophage infiltration in GC ( 39 ). HAVCR2 was reported to mediate T-cell depletion and immune dysfunction ( 40 ). Both immune checkpoint genes are overexpressed in GC tissues and predicts poor survival in GC patients.…”

Section: Discussionmentioning

confidence: 99%

A novel cuproptosis-related lncRNA nomogram to improve the prognosis prediction of gastric cancer

Feng

Chen

et al. 2022

Front. Oncol.

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BackgroundCuproptosis is a copper-triggered modality of mitochondrial cell death and cuproptosis process may play important roles in gastric cancer development. However, little is known about cuproptosis-related lncRNAs in gastric adenocarcinoma (STAD). This study is aimed to investigate the potential prognostic signatures of cuproptosis-related lncRNAs in STAD.MethodsThe Cancer Genome Atlas (TCGA) database were used to obtain gene expression profiles, clinicopathological, and OS information for STAD. Cuproptosis-related genes were collected based on previous studies and cuproptosis-related lncRNAs were screened out by co-expression analysis. The nomogram constructed by Cox regression analysis with the minimum absolute contraction and selection operator (lasso) algorithm. In addition, the potential response of ICB therapy and immune evasion incidence were estimated with Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Immune checkpoint expressions associated with risk scores were also analyzed. The correlation of immune checkpoint CD209 and HAVCR2 expressions associated with risk scores were experimentally testified by RT-qPCR, Western Blot, and IHC. ResultsPatients were classified into high-risk and low-risk groups based on the risk score calculated in this model. The Kaplan–Meier survival curve analysis revealed that the high-risk group was associated with poor prognosis. Multivariate Cox regression analysis suggested that this lncRNA prediction model was an independent risk factor affecting the OS rate. Furthermore, ROC curve indicates that the nomogram was superior to traditional clinicopathological features in predicting STAD prognosis. Finally, functional enrichment analysis and immune checkpoint investigation revealed that the nomogram is notably associated with cholesterol metabolism and immune functions, RT-qPCR and Western Blotting demonstrated the co-expression relationship of LINC01150 with CD209 and HAVCR2.ConclusionA novel cuproptosis-related lncRNAs signature impacts on the prognosis and immunological features of GC.

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Section: Discussionmentioning

confidence: 99%

A novel cuproptosis-related lncRNA nomogram to improve the prognosis prediction of gastric cancer

Feng

Chen

et al. 2022

Front. Oncol.

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“…These discrepancies might result from the different patterns of Tim-1 expression in distinct cell types; PBMCs are heterogeneous, with the highest proportion of T cells, and Tim-1 plays an important role in T-cell activation ( 26 ). Unlike Tim-1, Tim-3 suppresses the Th1 immune response ( 27 ). We also examined Tim-3 expression in different T-cell subsets and found that Tim-3 was mainly expressed in CD4 + T cells.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of Tim family molecules and an imbalanced ratio of Tim-3 to Tim-1 expression in patients with type 1 diabetes

Liu

Chen²,

Xiao³

et al. 2022

Front. Endocrinol.

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BackgroundT-cell immunoglobulin and mucin domain (Tim) proteins are immunomodulatory molecules that play key roles in the regulation of T-cell activation. Published studies have reported that Tim molecules are involved in the pathogenesis of certain autoimmune diseases. Type 1 diabetes (T1D) is an autoimmune disease in which T cells mediate the destruction of islet β cells. However, the expression of Tim molecules in T1D remains unclear. In this study, we measured the expression of Tim family molecules as well as T-cell subset-specific transcription factors in T1D patients, and we explored the possible involvement of Tim molecules in the pathogenesis of T1D.MethodsNinety T1D patients, Thirty-six type 2 diabetes (T2D) patients and forty healthy controls (HCs) were recruited for this study. Peripheral blood mononuclear cells (PBMCs) were isolated, RNA was extracted from the PBMCs and reverse transcribed into cDNA, and gene expression patterns were analysed by RT–qPCR. The expression of Tim molecules in different T-cell subsets was analysed by flow cytometry.ResultsCompared with that in HCs, the mRNA expression of Tim-1 and RORC was increased in T1D patients (P=0.0355 and P=0.0423, respectively), while the expression of Tim-3 was decreased (P=0.0013). In addition, compared with HCs, the ratio of Tim-3 to Tim-1 expression in diabetic patients was decreased (P<0.0001 for T1D and P=0.0387 for T2D). The ratios of T-Bet to GATA3 expression and RORC to FOXP3 expression were higher in T1D patients than in HCs (P=0.0042 and P=0.0066, respectively). Furthermore, the T1D patients with defective islet function had more significant imbalances in the Tim-3/Tim-1 and RORC/FOXP3 ratios (P<0.0001, and P=0.001, respectively). Moreover, Both Tim-3 expression in CD4+ T cells and the Tim-3 to Tim-1 ratio were elevated in T1D in the remission phase compared to T1D.ConclusionOur study revealed altered expression of Tim molecules in T1D patients. The imbalanced ratios of Tim-3/Tim-1 expression were more pronounced in T1D patients with defective islet function. However, alterations in Tim molecule expression are mitigated in T1D in the remission phase. All these findings suggest that Tim family molecules may be involved in the pathogenesis of T1D.

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“…LAG3 is a signi cant immune checkpoint with relevance in cancer, infectious disease, and autoimmunity (39). HAVCR2 encodes T-cell immunoglobulin mucin 3 protein, a critical checkpoint molecule found to be expressed on the surface of Th1 cells, acting as a negative regulator and binding to the ligand galectin-9 to mediate Th1 cell the apoptosis and regulating in ammatory responses (40). TIGIT is an inhibitory receptor expressed on lymphocytes that are recently propelled under the spotlight, which interacts with CD155 expressed on antigen-presenting cells or tumor cells to down-regulate T cell and natural killer (NK) cell functions (41).…”

Section: Discussionmentioning

confidence: 99%

Development and validation of immune-related genomics nomogram for prognostic prediction in left- and right-side colorectal cancer

Niu

Chen

et al. 2022

Preprint

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Background: Previous studies have reported that the tumor heterogeneity and immune molecular mechanisms of proximal and distal colorectal cancer (CRC) are divergent. Therefore, our study aims to analyze the difference between left-sided CRC (LCC) and right-sided CRC (RCC), and respectively develop the nomograms based on prognostic immune-related genes for LCC and RCC. Methods: We enrolled 443 colon cancer patients (220 LCC patients and 223 patients) from The Cancer Genome Atlas (TCGA) datasets. Firstly, the differential expressed immune-related genes (DE-IRGs), overall survival (OS), and biological functions between LCC and RCC groups were identified. Then, we analyzed the differences between the two groups in the immune microenvironment, immune checkpoint, and tumor mutation burden (TMB). Next, the LCC and RCC data from TCGA dataset are randomly divided into training and internal validation sets at a 7:3 ratio respectively. Additionally, 566 colon cancer patients (342 LCC patients and 224 RCC patients) in the GSE39582 dataset were downloaded from the Gene Expression Omnibus (GEO) database as the external validation set. Then, survival and Lasso Cox regression analyses were applied to identify hub immune-related genes and respectively establish two prognostic gene signatures of LCC and RCC groups. The prognostic signatures were validated by the 10-fold cross-validation, internal validation set, and external validation set. Further, combined with clinical features, we constructed two clinical predictive nomograms and validated them. Results: RCC patients have lower survival than LCC. RCC patients have higher proportions of T cells CD8, T cells follicular helper, and lower macrophages M0, T cells CD4 naive. RCC patients have higher ESTIMATE and immune scores and lower tumor purity. The immune checkpoint expression levels and TMB values are higher in RCC patients than in LCC. We respectively selected 10 immune-related genes for LCC and 7 genes for RCC groups to develop and validate the prognostic model and calculate a risk score for each patient. The AUC values of the risk score for OS in LCC were 0.735 in the training set, 0.711 in the internal validation set, and 0.744 in the external validation set, and in RCC were 0.704 in the training set, 0.738 in the internal validation set, and 0.705 in the external validation set. The AUC values of the 10-fold cross-validation range from 0.564 to 0.808 in LCC and from 0.589 to 0.792 in RCC. The nomogram of LCC of RCC includes risk based on prognostic genes, age, pathological T, N, M, stage, and gender. the AUC values of the LCC nomogram were 0.722 in the training set, 0.696 in the internal validation set, and 0.739 in the external validation set, and of the RCC nomogram were 0.774 in the training set, 0.744 in the internal validation set, and 0.737 in the external validation set. We also found that were significantly different between high- and low-risk patients in the immune score, ESTIMATE score, tumor purity, immune checkpoint expression levels, and TMB values. Conclusions: We found significant differences in the multidimensional insight between LCC and RCC patients in clinical features, DE-IRGs, TMB, immune checkpoint expression levels, and immune microenvironment landscape. Our study respectively established two prognostic nomograms based on DE-IRGs in combination with clinical features to provide a basis for personalized and precise treatment of LCC and RCC patients.

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TIM-3: An update on immunotherapy

Cited by 105 publications

References 84 publications

A novel cuproptosis-related lncRNA nomogram to improve the prognosis prediction of gastric cancer

A novel cuproptosis-related lncRNA nomogram to improve the prognosis prediction of gastric cancer

Altered expression of Tim family molecules and an imbalanced ratio of Tim-3 to Tim-1 expression in patients with type 1 diabetes

Development and validation of immune-related genomics nomogram for prognostic prediction in left- and right-side colorectal cancer

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