Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

Baba, Yoshifumi; Nomoto, Daichi; Okadome, Kazuo; Ishimoto, Takatsugu; Iwatsuki, Masaaki; Miyamoto, Yuji; Yoshida, Naoya; Baba, Hideo

doi:10.1111/cas.14541

Cited by 163 publications

(141 citation statements)

References 75 publications

Supporting

Mentioning

137

Contrasting

Order By: Relevance

“…Signals in immune microenvironment, including accumulation of tumor metabolites or T cell dysfunction, may significantly affect the response to immune checkpoint therapy (ICT) in EC patients (Wu et al, 2020). In recent years, the development of monoclonal antibodies against programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) has achieved convincing efficacy and clinical benefits in a variety of malignant tumors including ESCC (Yuan et al, 2017;Baba et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

Zhao

Xie

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

N6 methyladenosine (m6A) RNA methylation regulators play an important role in the development of tumors. However, their function in esophageal cancer (EC) has not been fully elucidated. Here, we analyzed the gene expression data of 24 major m6A RNA methylation regulators from 775 patients with EC from TCGA dataset. The present study showed the aberrations of m6A regulators in genome were correlated to prognosis in human ECs. Meanwhile, 17 m6A regulators showed increased expression in EC samples, including YTHDC1, IGF2BP2, FTO, METTL14, YTHDF3, RBM15, WTAP, HNRNPA2B1, HNRNPC, ALKBH5, YTHDF2, METTL16, IGF2BP3, VIRMA, RBM15B, YTHDF1, KIAA1429, HAKAI, and ZC3H13. Among them, we found HNRNPC, YTHDC2, WTAP, VIRMA, IGF2BP3, and HNRNPA2B1 were significantly correlated to worse outcomes and advanced stage in EC. Furthermore, we showed levels of m6A regulators is correlated with the expression of Immuno-regulators (Immunoinhibitors, Immunostimulators, and MHC molecules) and immune infiltration levels in EC. Bioinformatics further confirm m6A regulators were involved in regulating RNA splicing, RNA stability, and cell proliferation. Our study showed m6A regulators are promising targets and biomarkers for cancer immunotherapy in EC.

show abstract

Section: Introductionmentioning

confidence: 99%

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

Zhao

Xie

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…We found that PD-L1 (CD274) and CTLA4 show signi cantly higher expression in the TRAIL high group than in the TRAIL low group (Fig. 5a); however, PD-L1 (CD274) was predominantly expressed by tumors [28] while CTLA4 and LAG3 were mostly expressed by T cells in the tumor microenvironment [29]. Notably, a markedly positive correlation was observed between PD-L1 (CD274) and TRAIL (TNFSF10) in ESCC tissues (Fig.…”

Section: Trail Activates the Erk/stat3 Signaling Pathway To Induce Pdmentioning

confidence: 85%

TRAIL Promotes Epithelial-to-mesenchymal Transition by Inducing PD-L1 Expression in Esophageal Squamous Cell Carcinomas

Zhang

Qin

Yang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) was initially considered an immunity guard; however, its function remains controversial. Besides immune cells, lung and colon cancer cells have also been reported to express TRAIL, which can promote tumor invasion and metastasis. However, the biological function and underlying mechanism of action of TRAIL in esophageal squamous cell carcinoma (ESCC) remain poorly elucidated.Methods: The ESCC cells stemness, migration, and proliferation ability was assessed by sphere formation, Transwell, and CCK8 assay. The stemness- and EMT- related genes expression levels were analyzed by Western blot and RT-qPCR. The signal activation was conducted by Western blot. The PDX Model were performed to confirm our findings in vitro.Results: Herein, we found that TRAIL is a negative predictor in patients with ESCC. To further investigate the biological function of TRAIL, we established TRAIL knockdown and overexpression ESCC cell lines and found that TRAIL induced epithelial-mesenchymal transition (EMT) and promoted tumor aggressiveness. Furthermore, we demonstrated that TRAIL- overexpressing cells upregulated PD-L1 expression, which was dependent on the p-ERK/STAT3 signaling pathway. We obtained similar results when using recombinant human TRAIL. Finally, we validated the biological role and mechanism of action of TRAIL in vivo.Conclusions: These findings demonstrate that TRAIL promotes ESCC progression by enhancing PD-L1 expression, which induces EMT. This may explain the failure of TRAIL preclinical trials.Financial support: This work was supported by the National Key Research and Development (2018YFC1313400), the National Nature Science Foundation of China (U1804281, 91942314) and the National Science Fund for Distinguished Young Scholars (82001659).

show abstract

“…It has been confirmed that PD1, PDL1, and CTLA4 can be used as immune checkpoints for ESCC (Jiao et al, 2019;Baba et al, 2020). Here, Pearson correlation analysis was performed for the signature-based risk score and immune checkpoint expression to search for the potential function of the lncRNA signature in immunotherapy.…”

Section: Correlation Between Lncrna Signature and Immune Checkpointsmentioning

confidence: 98%

Immune-Related Long Non-coding RNA Signature and Clinical Nomogram to Evaluate Survival of Patients Suffering Esophageal Squamous Cell Carcinoma

Zhu

Wei

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Esophageal squamous cell carcinoma (ESCC) turns out to be one of the most prevalent cancer types, leading to a relatively high mortality among worldwide sufferers. In this study, gene microarray data of ESCC patients were obtained from the GEO database, with the samples involved divided into a training set and a validation set. Based on the immune-related differential long non-coding RNAs (lncRNAs) we identified, a prognostic eight-lncRNA-based risk signature was constructed following regression analyses. Then, the predictive capacity of the model was evaluated in the training set and validation set using survival curves and receiver operation characteristic curves. In addition, univariate and multivariate regression analyses based on clinical information and the model-based risk score also demonstrated the ability of the risk score in independently determining the prognosis of patients. Besides, based on the CIBERSORT tool, the abundance of immune infiltrates in tumor samples was scored, and a significant difference was presented between the high- and low- risk groups. Correlation analysis with immune checkpoints (PD1, PDL1, and CTLA4) indicated that the eight-lncRNA signature–based risk score was negatively correlated with PD1 expression, suggesting that the eight-lncRNA signature may have an effect in immunotherapy for ESCC. Finally, GO annotation was performed for the differential mRNAs that were co-expressed with the eight lncRNAs, and it was uncovered that they were remarkably enriched in immune-related biological functions. These results suggested that the eight-lncRNA signature–based risk model could be employed as an independent biomarker for ESCC prognosis and might play a part in evaluating the response of ESCC to immunotherapy with immune checkpoint blockade.

show abstract

Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

Cited by 163 publications

References 75 publications

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

TRAIL Promotes Epithelial-to-mesenchymal Transition by Inducing PD-L1 Expression in Esophageal Squamous Cell Carcinomas

Immune-Related Long Non-coding RNA Signature and Clinical Nomogram to Evaluate Survival of Patients Suffering Esophageal Squamous Cell Carcinoma

Contact Info

Product

Resources

About

Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

Cited by 163 publications

References 75 publications

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

TRAIL&nbsp;Promotes Epithelial-to-mesenchymal Transition by Inducing PD-L1 Expression in Esophageal Squamous Cell Carcinomas

Immune-Related Long Non-coding RNA Signature and Clinical Nomogram to Evaluate Survival of Patients Suffering Esophageal Squamous Cell Carcinoma

Contact Info

Product

Resources

About

TRAIL Promotes Epithelial-to-mesenchymal Transition by Inducing PD-L1 Expression in Esophageal Squamous Cell Carcinomas