Dataset Information

Tumor Niche Network-Defined Subtypes Predict Immunotherapy Response of Esophageal Squamous Cell Cancer.

ABSTRACT: Despite the promising outcomes of immune checkpoint blockade (ICB), resistance to ICB presents a new challenge. Therefore, selecting patients for specific ICB applications is crucial for maximizing therapeutic efficacy. Herein we curated 69 human esophageal squamous cell cancer (ESCC) patients' tumor microenvironment (TME) single-cell transcriptomic datasets to subtype ESCC. Integrative analyses of the cellular network transcriptional signatures of T cells, myeloid cells, and fibroblasts define distinct ESCC subtypes characterized by T cell exhaustion, Interferon (IFN) a/b signaling, TIGIT enrichment, and specific marker genes. Furthermore, this approach classifies ESCC patients into ICB responders and non-responders, as validated by liquid biopsy single-cell transcriptomics. Our study stratifies ESCC patients based on TME transcriptional network, providing novel insights into tumor niche remodeling and predicting ICB responses in ESCC patients.

SUBMITTER: Ko KP

PROVIDER: S-EPMC9949073 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Tumor Niche Network-Defined Subtypes Predict Immunotherapy Response of Esophageal Squamous Cell Cancer.

Ko Kyung-Pil KP Zhang Shengzhe S Huang Yuanjian Y Kim Bongjun B Zou Gengyi G Jun Sohee S Zhang Jie J Martin Cecilia C Dunbar Karen J KJ Efe Gizem G Rustgi Anil K AK Zhang Haiyang H Nakagawa Hiroshi H Park Jae-Il JI

bioRxiv : the preprint server for biology 20230215

Despite the promising outcomes of immune checkpoint blockade (ICB), resistance to ICB presents a new challenge. Therefore, selecting patients for specific ICB applications is crucial for maximizing therapeutic efficacy. Herein we curated 69 human esophageal squamous cell cancer (ESCC) patients' tumor microenvironment (TME) single-cell transcriptomic datasets to subtype ESCC. Integrative analyses of the cellular network transcriptional signatures of T cells, myeloid cells, and fibroblasts define ...[more]

PMID: 36824935

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Project description:Purpose: The applicability of mRNA vaccines against esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we identified potential antigens for developing mRNA vaccines against ESCC and characterized immune subtypes to select appropriate patients for vaccination. Methods: RNA-seq, genetic alteration data, and corresponding clinical information of ESCC patients were obtained from the Cancer Genome Atlas (TCGA) database. The RNA-seq data of normal esophageal tissue were obtained from the Genotype-Tissue Expression (GTEx) database. Potential tumor antigens were screened by analyzing differentially expressed and mutated genes and potential antigens with significant differences in prognosis were screened using the Kaplan-Meier method. The proportion of immune cell infiltration in the tumor microenvironment was estimated using CIBERSORT and MCPcounter, and the correlation of potential antigens with antigen-presenting cells and major histocompatibility complex class II was analyzed. Subsequently, immune subtypes were constructed using consensus clustering analysis and characterized by single-sample gene set enrichment analysis and weighted gene co-expression network analysis (WGCNA). The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to analyze the drug sensitivity of different immune subtypes. Results: Four overexpressed and mutated tumor antigens associated with antigen presentation and poor prognosis were identified in ESCC, including NLRC5, FCRL4, TMEM229B, and LCP2. By consensus clustering, we identified two immune-associated ESCC subtypes, immune subtype 1 (IS1) and immune subtype 2 (IS2); the prognosis of the two subtypes was statistically different. In addition, the two immune subtypes had distinctly different cellular, molecular, and clinical characteristics. IS1 patients have a distinct immune "hot" phenotype with strong immune tolerance, whereas patients with IS2 have an immune "cold" phenotype. Differential expression of immune checkpoints and immunogenic cell death modulators was observed between the different immune subtypes. Finally, we found that IS1 and IS2 patients showed different drug sensitivities to common anti-tumor drugs, possibly facilitating the development of individualized treatment regimens for patients. Conclusion: NLRC5, LCP2, TMEM229B, and FCRL4 are potential antigens for ESCC mRNA vaccines, and such vaccines may be more suitable for IS2 patients. This study provides a theoretical basis for mRNA vaccines against ESCC, by identifying the critical characteristics to predict ESCC prognosis and select suitable patients for vaccination.

Dataset Information

Tumor Niche Network-Defined Subtypes Predict Immunotherapy Response of Esophageal Squamous Cell Cancer.

Publications

Tumor Niche Network-Defined Subtypes Predict Immunotherapy Response of Esophageal Squamous Cell Cancer.

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