The immune microenvironment features and response to immunotherapy in EBV-associated lymphoepithelioma-like cholangiocarcinoma

Chiang, Nai‐Jung; Hou, Ya–Chin; Tan, Kien Thiam; Tsai, Hung‐Wen; Lin, Ying‐Ting; Yeh, Yi‐Chen; Chen, Li-Tzong; Hou, Ya-Fu; Chen, Ming-Huang; Shan, Yan-Shen

doi:10.1007/s12072-022-10346-3

Cited by 15 publications

(5 citation statements)

References 28 publications

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“…The high ICD subgroup is associated with a better prognosis and higher levels of immune cell infiltration than the low ICD subgroup. Some studies have reported better efficacy of tumor-applied immunosuppression when suppressor receptors are highly expressed ( 28 ), which is consistent with our findings. Among the different subtypes of ICD, the frequency of mutations was slightly higher in the high ICD subtype than in the low subtype group.…”

Section: Discussionsupporting

confidence: 93%

Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma

et al. 2022

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Although immune checkpoint inhibitors have improved the overall survival rate of skin cutaneous melanoma (SKCM) patients, there is a wide variation and low response rate to these treatments in clinical immunotherapy for melanoma patients. These problems can be addressed through the induction of immunogenic cell death (ICD).We constructed an ICD-based prognostic model to predict the prognosis of SKCM patients and the efficacy of immunotherapy. Information on melanoma and normal samples obtained by TCGA and GTEx was stratified by ICD-related genes. The samples were divided into two subtypes according to high and low expression of ICD using an unsupervised clustering method (K-means). Patients with ICD-high subtype showed longer overall survival. We found that the ICD-related differential genes were associated with several cell death and immune-related pathways through GO, KEGG and GSEA. Immunoscore and tumor purity of ICD-associated genes was calculated using ESTIMATE, and ICD-high subtypes had higher immunoscore and lower tumor purity than ICD-low subtypes. Seven ICD-associated genes were obtained by one-way Cox regression and Lasso regression of ICD genes. Risk models were constructed to classify melanoma patients into high- risk and low-risk groups. The expression of ICD-related pivotal genes was lower in the high-risk group than in the low-risk group, and the survival time was significantly higher in the low-risk group than in the high-risk group. We then found that ICD risk characteristics had predictive value for the clinical efficacy of immunotherapy, with higher ICD risk scores in the immunotherapy non-responsive group. Combined with clinicopathological factors, a nomogram was established. the ROC and calibration curves assessed the ability of the nomogram to predict prognosis. We developed a new classification system for SKCM based on the characteristics of ICDs. This stratification has important clinical implications for estimating the prognosis and immunotherapy of SKCM patients.

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Section: Discussionsupporting

confidence: 93%

Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma

et al. 2022

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“…Various cells with viral infections are capable of producing type I interferon response [ 44 , 45 ], which attracts abundant immune cell infiltration. Not surprisingly, EBV-related tumors are characterized as immune “hot” tumors with a strong adaptive immune response [ 46 , 47 , 48 ]. However, increasing immune cell infiltration in tumors by artificial EBV infections would not be ethical.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Apolipoprotein L6 Improves Tumor Immunotherapy by Inducing Immunogenic Cell Death

Liu

Chen

et al. 2023

Biomolecules

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In the past few years, immune checkpoint blockade (ICB) therapy has emerged as a breakthrough treatment for cancers and has demonstrated inspiring effects in tumor patients with Epstein-Barr virus (EBV) infection. To allow more patients to benefit from immunotherapy, exploring novel biomarkers based on EBV-related tumors and immunotherapy cohorts was pursued in the present study. The essential biomarkers that may enhance antitumor immunity across EBV-related tumors were identified using the large-scale transcriptomic profiles of EBV-associated tumors and tumor immunotherapy cohorts. The clinical significance of vital genes was evaluated in multiple tumor immunotherapy cohorts. Moreover, the potential function of essential genes in immunotherapy was explored via bioinformatic analyses and verified by qRT-PCR, Western blot analysis, CCK8 assay and flow cytometry. Apolipoprotein L6 (APOL6) was considered the essential biomarker for enhancing antitumor immunity across EBV-positive tumors. The upregulation of APOL6 was correlated with increased response rates and prolonged survival in multiple tumor immunotherapy cohorts. Bioinformatic analyses suggested that APOL6 may enhance tumor immunotherapy by inducing immunogenic cell death. Pancreatic cancer cells transfected with APOL6 overexpression plasmid underwent apoptosis, necroptosis, and pyroptosis with immunogenic features. The biomarker upregulated in EBV-related tumors could further elucidate the drivers of immunotherapy response. The upregulation of APOL6 could improve immunotherapy by triggering immunogenic cell death, thus offering a new target to optimize cancer immunotherapy.

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“…Rokutan et al [43] observed MUC6 mutating in 20% of gastric dysplasia/intraepithelial neoplasia samples. Moreover, MUC6 mutations were found in Epstein-Barr virus (EBV)associated lymphoepithelioma-like cholangiocarcinoma [44], and directly associated with thyroid cancer [45]. On the other hand, the mutation status of MUC6 and three other genes (ATR, ERBB3 and KDR) was obtained as a marker for the recurrence of non-small-cell lung cancer (NSCLC) patients [46].…”

Section: Discussionmentioning

confidence: 99%

Sequencing Analysis of MUC6 and MUC16 Gene Fragments in Patients with Oropharyngeal Squamous Cell Carcinoma Reveals Novel Mutations: A Preliminary Study

Gaździcka

Biernacki

Salatino

et al. 2023

CIMB

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The growing incidence of oropharyngeal squamous cell carcinoma (OPSCC) calls for better understanding of the mutational landscape of such cases. Mucins (MUCs) are multifunctional glycoproteins expressed by the epithelial cells and may be associated with the epithelial tumour invasion and progression. The present study aimed at the analysis of the sequence of selected MUC6 and MUC16 gene fragments in the tumour, as well as the margin, samples obtained from 18 OPSCC patients. Possible associations between the detected mutations and the clinicopathological and demographic characteristics of the study group were analysed. Sanger sequencing and bioinformatic data analysis of the selected MUC6 and MUC16 cDNA fragments were performed. Our study found 13 and 3 mutations in MUC6 and MUC16, respectively. In particular, one novelty variant found that the MUC6 gene (chr11:1018257 A>T) was the most frequent across our cohort, in both the tumour and the margin samples, and was then classified as a high impact, stop-gain mutation. The current study found novel mutations in MUC6 and MUC16 providing new insight into the genetic alternation in mucin genes among the OPSCC patients. Further studies, including larger cohorts, are recommended to recognise the pattern in which the mutations affect oropharyngeal carcinogenesis.

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The immune microenvironment features and response to immunotherapy in EBV-associated lymphoepithelioma-like cholangiocarcinoma

Cited by 15 publications

References 28 publications

Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma

Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma

Upregulation of Apolipoprotein L6 Improves Tumor Immunotherapy by Inducing Immunogenic Cell Death

Sequencing Analysis of MUC6 and MUC16 Gene Fragments in Patients with Oropharyngeal Squamous Cell Carcinoma Reveals Novel Mutations: A Preliminary Study

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