The CD70-CD27 axis in oncology: the new kids on the block

Flieswasser, Tal; Eynde, Astrid Van den; Audenaerde, Jonas R.M. Van; Waele, Jorrit De; Lardon, Filip; Riether, Carsten; Haard, Hans de; Smits, Elke; Pauwels, Patrick; Jacobs, Julie

doi:10.1186/s13046-021-02215-y

Cited by 81 publications

(70 citation statements)

References 150 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, STAT4, CCR7, ARHGAP15, and CD27 were selected as the hub genes to distinguish the different subtypes of PDAC patients. In general, these four genes are all related to the development, maturation, or function of Th1 cells (Oestreich and Weinmann, 2012;Margraf et al, 2020;Salem et al, 2021;Flieswasser et al, 2022). They may affect the prognosis of PDAC patients in many aspects.…”

Section: Discussionmentioning

confidence: 99%

Type 1 T Helper Cell-Based Molecular Subtypes and Signature Are Associated with Clinical Outcome in Pancreatic Ductal Adenocarcinoma

Wei

Zhang

Cao

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC) is shown to be related with poor prognosis. To construct an immune-related gene prognostic risk model for PDAC and clarify the molecular and immune characteristics and the benefit of immune checkpoint inhibitor (ICI) therapy in prognostic risk model-defined subgroups of PDAC, we analyze the association between the density of immune cell infiltration and lymph node metastatic status and further study the potential role of immune cells, immune cell–related genes, and immunotherapy outcomes in PDAC patients using bioinformatics models and machine learning methods. Based on The Cancer Genome Atlas (TCGA), PACA-AU and PACA-CA data sets, 62 immune-related hub genes were identified by weighted gene co-expression network analysis (WGCNA). Four genes were selected to construct a molecular subtype identification based on the type 1 T helper cell–related hub genes by using the Cox regression method. We found that lower type 1 T helper cell abundance was correlated with prolonged survival in PDAC patients. Further, prognostic risk score model constructed with the type 1 T helper cell-related signature showed high accuracy in predicting overall survival and response to immunotherapy. This study might improve the understanding of the role of type 1 T helper cells in PDAC patients and aid in the development of immunotherapy and personalized treatments for these patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Type 1 T Helper Cell-Based Molecular Subtypes and Signature Are Associated with Clinical Outcome in Pancreatic Ductal Adenocarcinoma

Wei

Zhang

Cao

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Therefore, treatments targeting CD70 have great potential for treating both early and advanced cancers. However, some studies have shown that CD70 is not up-regulated or not signi cantly up-regulated in tumor cells from Kaposi's sarcoma, prostate cancer, Langerhans cell histiocytosis, and colorectal cancer [14,31]. Although CD70 is prevalent in many cancers, the expression pattern of CD70 varies in terms of spatial distribution, expression intensity, and percentage of positive cells.…”

Section: Discussionmentioning

confidence: 99%

“…Given this, developing new immunotherapy targets may be a more effective and promising therapeutic strategy. Thus, the CD70-CD27 axis, which belongs to the tumor necrosis factor (TNF) superfamily, has emerged as an appealing target for tumor development [13,14]. CD70 and CD27 are TNF ligand and receptor family ligand-receptor pairs that are critical for T cell co-stimulation [15].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer

Kong

Xiong

2023

Funct Integr Genomics

View full text Add to dashboard Cite

The immune checkpoint molecule CD70 and its receptor CD27 constitute the signal transduction axis, which is abnormally expressed in many solid tumors and is crucial for T cell co-stimulation and immune escape. Tumor cells regulate the expression of CD27 by expressing CD70 in tumor microenvironment and promote immune escape.The discovery of the immunosuppressive effect of the CD70-CD27 signaling axis on tumor cells introduces a new anti-tumor immunotherapy -CD70. Although current research evidence suggests a link between CD70 and tumors, no pan-cancer analysis is available. Using the Cancer Genome Atlas and Gene Expression Omnibus datasets, we rst explored the potential carcinogenic role of the CD70-CD27 signaling axis in human malignancies. CD70 expression is up-regulated in most cancers and has an obvious correlation with the prognosis of tumor patients. The expression of CD70 and CD27 is associated with the level of regulatory T cells (Tregs) in ltration. In addition, T cell receptor signaling pathways, PI3K-Akt, NF-κB, and TNF signaling pathways are also involved in CD70-mediated immune escape. CD70 mainly regulates tumor immune escape by regulating T cell-mediated tumor killing, while Tregs may be its main T cell subset. Our rst pan-cancer study provides a relatively comprehensive understanding of the carcinogenic role of the CD70-CD27 signaling axis in different tumors.

show abstract

“…CD27 is a promising target of immunotherapy. CD27 is a stimulatory immune checkpoint mainly found on the surface of immune cells, which is the receptor of CD70 ( 18 ). Soluble CD27 is a 32kDa cleaved isoform of membrane-bound CD27, which has been reported to interfere interaction of CD27 and CD70 ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Soluble Immune Checkpoint-Related Proteins in Blood Are Associated With Invasion and Progression in Non-Small Cell Lung Cancer

Wang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

BackgroundImmune checkpoint inhibition therapy has been achieved significant success in the treatment of non-small cell lung cancer (NSCLC). However, the role of soluble immune checkpoint- related proteins in NSCLC remains obscure.MethodsWe evaluated the circulating levels of 14 immune checkpoint-related proteins panel (BTLA, LAG-3, GITR, IDO, PD-L2, PD-L1, PD-1, HVEM, Tim-3, CD28, CD27, CD80, CD137 and CTLA-4) and their associations with the risk of invasive disease and the risk of NSCLC in 43 pre-invasive (AIS), 81 invasive NSCLC (IAC) patients and matched 35 healthy donors using a multiplex Luminex assay. Gene expression in tumors from TCGA were analyzed to elucidate potential mechanisms. The multivariate logistic regression model was applied in the study. ROC(receiver operator characteristic) curve and calibration curve were used in the performance evaluation.ResultsWe found that sCD27, sCD80, CD137 and sPDL2 levels were significantly increased in IAC cases compared to AIS cases (P= 1.05E-06, 4.44E-05, 2.30E-05 and 1.16E-06, respectively), whereas sPDL1 and sPDL2 levels were significantly increased in NSCLC cases compared to healthy controls (P=3.25E-05 and 1.49E-05, respectively). Unconditional univariate logistic regression analysis indicated that increased sCD27, sCD80, sCD137, and sPDL2 were significantly correlated with the risk of invasive diseases. The model with clinical variables, sCD27 and sPDL2 demonstrated the best performance (AUC=0.845) in predicting the risk of IAC. CD27 and PDCD1LG2 (PDL2) showed significant association with cancer invasion signature in TCGA dataset.ConclusionOur study provides evidence that soluble immune checkpoint-related proteins may associate with the risk of IAC, and we further established an optimized multivariate predictive model, which highlights their potential application in the treatment of NSCLC patients. Future studies may apply these biomarkers to test their predictive value of survival and treatment outcome during immunotherapy in NSCLC patients.

show abstract

The CD70-CD27 axis in oncology: the new kids on the block

Cited by 81 publications

References 150 publications

Type 1 T Helper Cell-Based Molecular Subtypes and Signature Are Associated with Clinical Outcome in Pancreatic Ductal Adenocarcinoma

Type 1 T Helper Cell-Based Molecular Subtypes and Signature Are Associated with Clinical Outcome in Pancreatic Ductal Adenocarcinoma

Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer

Soluble Immune Checkpoint-Related Proteins in Blood Are Associated With Invasion and Progression in Non-Small Cell Lung Cancer

Contact Info

Product

Resources

About