Metabolic modulation of immune checkpoints and novel therapeutic strategies in cancer

Wang, Yi; Wang, Yuya; Ren, Yifei; Zhang, Qi; Yi, Ping; Cheng, Chunming

doi:10.1016/j.semcancer.2022.02.010

Cited by 89 publications

(63 citation statements)

References 373 publications

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“…T cell activation requires co-stimulation via engagement of CD28 on the T cell with CD80/86 on the APC. Cytotoxic T lymphocyte–associated protein 4 (CTLA4) is a competitive inhibitor of CD80/86 that downregulates T cell responses ( 210 ). This T cell suppressive activity served to engineer a human IgG heavy chains coupled with CTLA4 to create a fusion antibody able to prevent graft rejection ( 211 ).…”

Section: The Prevention Of Xenotransplantation Rejectionmentioning

confidence: 99%

Current status of xenotransplantation research and the strategies for preventing xenograft rejection

Zhou

Wang

et al. 2022

Front. Immunol.

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Transplantation is often the last resort for end-stage organ failures, e.g., kidney, liver, heart, lung, and pancreas. The shortage of donor organs is the main limiting factor for successful transplantation in humans. Except living donations, other alternatives are needed, e.g., xenotransplantation of pig organs. However, immune rejection remains the major challenge to overcome in xenotransplantation. There are three different xenogeneic types of rejections, based on the responses and mechanisms involved. It includes hyperacute rejection (HAR), delayed xenograft rejection (DXR) and chronic rejection. DXR, sometimes involves acute humoral xenograft rejection (AHR) and cellular xenograft rejection (CXR), which cannot be strictly distinguished from each other in pathological process. In this review, we comprehensively discussed the mechanism of these immunological rejections and summarized the strategies for preventing them, such as generation of gene knock out donors by different genome editing tools and the use of immunosuppressive regimens. We also addressed organ-specific barriers and challenges needed to pave the way for clinical xenotransplantation. Taken together, this information will benefit the current immunological research in the field of xenotransplantation.

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Section: The Prevention Of Xenotransplantation Rejectionmentioning

confidence: 99%

Current status of xenotransplantation research and the strategies for preventing xenograft rejection

Zhou

Wang

et al. 2022

Front. Immunol.

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“…In the tumor microenvironment, infiltrating immune cells experience functional impairment by expressing multiple inhibitory signals on the cell surface, such as PD-1/PD-L1, CTLA-4, TIGIT, and TIM-3, leading to tumor immunosuppression. These inhibitory signals are also known as immune checkpoints (33). PD-1/ PD-L1 is among the earliest used in treating advanced melanoma (34).…”

Section: Discussionmentioning

confidence: 99%

DCBLD1 Overexpression Is Associated With a Poor Prognosis in Head and Neck Squamous Cell Carcinoma

Yan²,

Ma³

et al. 2022

Front. Immunol.

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BackgroundDCBLD1 is highly expressed in several kinds of cancer and plays a potential prognostic factor. However, the prognostic value and immune infiltration in head and neck squamous cell carcinoma remain unclear and need further research.Materials and MethodsDCBLD1 expression and clinical information were obtained from the Cancer Genome Atlas (TCGA) database. The mRNA level in cell lines (SCC25 and CAL27) and gingival fibroblasts were detected using quantitative PCR. Cox regression analysis was used to evaluate the prognostic values of DCBLD1 and clinical data in HNSCC. A nomogram was also established to predict the impact of DCBLD1 on prognosis based on Cox multivariate results. The methylation level of DCBLD1 in HNSC and its prognosis were analyzed in UALACN and MethSurv. Finally, the potential biological functions of DCBLD1 were investigated using gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA).ResultsThe mRNA and protein expression levels of DCBLD1 were highly expressed in HNSCC tissue and cell lines. The Cox analyses demonstrate that highly expressed DCBLD1 is an independent prognosis marker (p < 0.05). ROC curve analysis showed the performance of DCBLD1 (area under the ROC curve: 0.948, sensitivity: 93.2%, specificity: 84.7%). The methylation was increased in HNSCC patients compared with normal subjects (p < 0.05) and was associated with poor prognosis at sites cg27642470 and cg21104965. Additionally, DCBLD1 expression is poorly associated with immune cell infiltration and immunological checkpoints PD-L1 and TIM-3.ConclusionIn head and neck squamous cell carcinoma, DCBLD1 is overexpressed, associated with poor patient prognosis. The detailed underlying mechanism merits further research.

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“…In our study, we revealed that the high-risk group was infiltrated with significantly higher degrees of antitumour immune cells (e.g., CD8 T cells) than the low-risk group, indicating that the high-risk group lesions belonged to an immune-inflamed phenotype. Major regulators of immune infiltration include TMB and cellular metabolism ( Wang et al, 2022 ). TMB is positively correlated with neoantigens, which are recognized as key drivers of immune infiltration ( Chalmers et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolism-Associated DNA Methylation Signature Stratifies Lower-Grade Glioma Patients and Predicts Response to Immunotherapy

Yang

Shan

Zhao

et al. 2022

Front. Cell Dev. Biol.

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Metabolism and DNA methylation (DNAm) are closely linked. The value of the metabolism-DNAm interplay in stratifying glioma patients has not been explored. In the present study, we aimed to stratify lower-grade glioma (LGG) patients based on the DNAm associated with metabolic reprogramming. Four data sets of LGGs from three databases (TCGA/CGGA/GEO) were used in this study. By screening the Kendall’s correlation of DNAm with 87 metabolic processes from KEGG, we identified 391 CpGs with a strong correlation with metabolism. Based on these metabolism-associated CpGs, we performed consensus clustering and identified three distinct subgroups of LGGs. These three subgroups were characterized by distinct molecular features and clinical outcomes. We also constructed a subgroup-related, quantifiable CpG signature with strong prognostic power to stratify LGGs. It also serves as a potential biomarker to predict the response to immunotherapy. Overall, our findings provide new perspectives for the stratification of LGGs and for understanding the mechanisms driving malignancy.

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Metabolic modulation of immune checkpoints and novel therapeutic strategies in cancer

Cited by 89 publications

References 373 publications

Current status of xenotransplantation research and the strategies for preventing xenograft rejection

Current status of xenotransplantation research and the strategies for preventing xenograft rejection

DCBLD1 Overexpression Is Associated With a Poor Prognosis in Head and Neck Squamous Cell Carcinoma

Metabolism-Associated DNA Methylation Signature Stratifies Lower-Grade Glioma Patients and Predicts Response to Immunotherapy

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