Identification of tumor antigens and immune subtypes of cholangiocarcinoma for mRNA vaccine development

Huang, Xing; Tang, Tianyu; Zhang, Gang; Liang, Tingbo

doi:10.1186/s12943-021-01342-6

Cited by 100 publications

(91 citation statements)

References 42 publications

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“…1 c). This kind of classification has been described by Huang et al [ 2 , 28 ] in studies of cholangiocarcinoma and pancreatic adenocarcinoma. These four subgroups have typical differences in immune characteristics.…”

Section: Resultsmentioning

confidence: 97%

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

et al. 2021

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Background Hepatocellular carcinoma (HCC) has a poor prognosis and has become the sixth most common malignancy worldwide due to its high incidence. Advanced approaches to therapy, including immunotherapeutic strategies, have played crucial roles in decreasing recurrence rates and improving clinical outcomes. The HCC microenvironment is important for both tumour carcinogenesis and immunogenicity, but a classification system based on immune signatures has not yet been comprehensively described. Methods HCC datasets from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the International Cancer Genome Consortium (ICGC) were used in this study. Gene set enrichment analysis (GSEA) and the ConsensusClusterPlus algorithm were used for clustering assessments. We scored immune cell infiltration and used linear discriminant analysis (LDA) to improve HCC classification accuracy. Pearson's correlation analyses were performed to assess relationships between immune signature indices and immunotherapies. In addition, weighted gene co-expression network analysis (WGCNA) was applied to identify candidate modules closely associated with immune signature indices. Results Based on 152 immune signatures from HCC samples, we identified four distinct immune subtypes (IS1, IS2, IS3, and IS4). Subtypes IS1 and IS4 had more favourable prognoses than subtypes IS2 and IS3. These four subtypes also had different immune system characteristics. The IS1 subtype had the highest scores for IFNγ, cytolysis, angiogenesis, and immune cell infiltration among all subtypes. We also identified 11 potential genes, namely, TSPAN15, TSPO, METTL9, CD276, TP53I11, SPINT1, TSPO, TRABD2B, WARS2, C9ORF116, and LBH, that may represent potential immunological biomarkers for HCC. Furthermore, real-time PCR revealed that SPINT1, CD276, TSPO, TSPAN15, METTL9, and WARS2 expression was increased in HCC cells. Conclusions The present gene-based immune signature classification and indexing may provide novel perspectives for both HCC immunotherapy management and prognosis prediction.

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Section: Resultsmentioning

confidence: 97%

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

et al. 2021

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“…Herein, we utilized the IPS to determine the association between immune subtypes and immune response. Additionally, the tumor mutational burden (TMB) was assessed for the immune three subtypes in view of its close relationship with immunotherapeutic efficacy (24,25). The mutations in each patient were calculated using the TCGA mutect2-processed mutation data.…”

Section: Association Between Immune Subtypes and Mutational Statusmentioning

confidence: 99%

Dissecting Tumor Antigens and Immune Subtypes of Glioma to Develop mRNA Vaccine

et al. 2021

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BackgroundNowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. However, its application against glioma is still in its infancy. In this study, the applicable candidates were excavated for mRNA vaccine treatment in the perspective of immune regulation, and suitable glioma recipients with corresponding immune subtypes were further investigated.MethodsThe RNA-seq data and clinical information of 702 and 325 patients were recruited from TCGA and CGGA, separately. The genetic alteration profile was visualized and compared by cBioPortal. Then, we explored prognostic outcomes and immune correlations of the selected antigens to validate their clinical relevance. The prognostic index was measured via GEPIA2, and infiltration of antigen-presenting cells (APCs) was calculated and visualized by TIMER. Based on immune-related gene expression, immune subtypes of glioma were identified using consensus clustering analysis. Moreover, the immune landscape was visualized by graph learning-based dimensionality reduction analysis.ResultsFour glioma antigens, namely ANXA5, FKBP10, MSN, and PYGL, associated with superior prognoses and infiltration of APCs were selected. Three immune subtypes IS1–IS3 were identified, which fundamentally differed in molecular, cellular, and clinical signatures. Patients in subtypes IS2 and IS3 carried immunologically cold phenotypes, whereas those in IS1 carried immunologically hot phenotype. Particularly, patients in subtypes IS3 and IS2 demonstrated better outcomes than that in IS1. Expression profiles of immune checkpoints and immunogenic cell death (ICD) modulators showed a difference among IS1–IS3 tumors. Ultimately, the immune landscape of glioma elucidated considerable heterogeneity not only between individual patients but also within the same immune subtype.ConclusionsANXA5, FKBP10, MSN, and PYGL are identified as potential antigens for anti-glioma mRNA vaccine production, specifically for patients in immune subtypes 2 and 3. In summary, this study may shed new light on the promising approaches of immunotherapy, such as devising mRNA vaccination tailored to applicable glioma recipients.

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“…The expression level of immunogenic cell death modulators (ICDs) obtained from previous studies (Huang et al, 2021) and vital immune check points (Cimen Bozkus et al, 2019), PDCD1 (PD1), CD274 (PD-L1), and CTLA4, were compared among different immune subtypes by Pairwise t-tests. Furthermore, we compared the distribution of tumor mutational burden (TMB) between the immune groups.…”

Section: Differential Analysis Of Icds Tmb and Icpsmentioning

confidence: 99%

Identification of Tumor Antigens and Immune Landscape in Glioblastoma for mRNA Vaccine Development

Wang

Yang

et al. 2021

Front. Genet.

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Background: Clinical benefits from standard therapies against glioblastoma (GBM) are limited in part due to the intrinsic radio- and chemo-resistance. As an essential part of tumor immunotherapy for adjunct, therapeutic tumor vaccines have been effective against multiple solid cancers, while their efficacy against GBM remains undefined. Therefore, this study aims to find the possible tumor antigens of GBM and identify the suitable population for cancer vaccination through immunophenotyping.Method: The genomic and responding clinical data of 169 GBM samples and five normal brain samples were obtained from The Cancer Genome Atlas (TCGA). The mRNA_seq data of 940 normal brain tissue were downloaded from Genotype-Tissue Expression (GTEx). Potential GBM mRNA antigens were screened out by differential expression, copy number variant (CNV), and mutation analysis. K-M survival and Cox analysis were carried out to investigate the prognostic association of potential tumor antigens. Tumor Immune Estimation Resource (TIMER) was used to explore the association between the antigens and tumor immune infiltrating cells (TIICs). Immunophenotyping of 169 samples was performed through consensus clustering based on the abundance of 22 kinds of immune cells. The characteristics of the tumor immune microenvironment (TIME) in each cluster were explored through single-sample gene set enrichment analysis based on 29 kinds of immune-related hallmarks and pathways. Weighted gene co-expression network analysis (WGCNA) was performed to cluster the genes related to immune subtypes. Finally, pathway enrichment analyses were performed to annotate the potential function of modules screened through WGCNA.Results: Two potential tumor antigens selected were significantly positively associated with the antigen-presenting immune cells (APCs) in GBM. Furthermore, the expression of antigens was verified at the protein level by Immunohistochemistry. Two robust immune subtypes, immune subtype 1 (IS1) and immune subtype 2 (IS2), representing immune status “immune inhibition” and “immune inflamed”, respectively, had distinct clinical outcomes in GBM.Conclusion: ARPC1B and HK3 were potential mRNA antigens for developing GBM mRNA vaccination, and the patients in IS2 were considered the most suitable population for vaccination in GBM.

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Identification of tumor antigens and immune subtypes of cholangiocarcinoma for mRNA vaccine development

Cited by 100 publications

References 42 publications

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

Dissecting Tumor Antigens and Immune Subtypes of Glioma to Develop mRNA Vaccine

Identification of Tumor Antigens and Immune Landscape in Glioblastoma for mRNA Vaccine Development

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