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Updated: Aug 19, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Integrated multi-omics analysis identifies CD73 as a prognostic biomarker and immunotherapy response predictor in
Ao Shen1,2, Yafen Ye3, Fan Chen1,2,4
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Background:
Advances in tumor immunotherapy have been developed for patients with advanced recurrent or metastatic (R/M) HNSCC. However, the response of most HNSCC patients to immune checkpoint inhibitors (ICI) remains unsatisfactory. CD73 is a promising target for tumor immunotherapy, but its role in HNSCC remains insufficient. In this study, we aim to explore the function of CD73 in HNSCC.
Methods:
Transcriptomic and clinical data of TCGA-HNSC were downloaded from UCSC Xena for analysis of CD73 mRNA expression and prognosis. Immunohistochemical assay were performed to validate the expression of CD73 in tumor tissues and its relationship with CD8+ T cells. GSEA analysis was performed with the "clusterProfiler" R package. Immune infiltration analysis was calculated with ESTIMATE, CIBERSORT and MCP-counter algorithms. Single-cell transcriptomic data was originated from GSE103322. Cell clustering, annotation and CD73 expression were from the TISCH database. Correlation data between CD73 and tumor signatures were obtained from the CancerSEA database. Somatic mutation data were obtained from TCGA-HNSC and analyzed by "maftools" R package. Immune efficacy prediction was performed using TIDE algorithm and validated with the IMvigor210 cohort.
Results:
Compared with normal tissues, both mRNA and protein expressions of CD73 were elevated in tumor tissues (P = 9.7×10-10, P = 7.6×10-5, respectively). Kaplan-Meier analysis revealed that patients with high expression of CD73 had worse overall survival (log-rank P = 0.0094), and CD73 could be used as a diagnostic factor for HNSCC (AUC = 0.778). Both bulk RNA-seq and single-cell RNA-seq analysis showed that high CD73 expression can promote EMT and metastasis, samples with high CD73 expression had reduced CD8+ T cells. Furthermore, it was found that CD73-high group was more prone to have mutations in TP53, HRAS and CDKN2A, and were negatively correlated with TMB (P = 0.0055) and MSI (P = 0.00034). Mutational signature analysis found that CD73 was associated with APOBEC signature. Immunotherapy efficacy analysis showed that CD73-high group was less sensitive to immune efficacy.
Conclusions:
Our results demonstrate that CD73 has an inhibitory effect on the tumor microenvironment, and is more likely to be unresponsive to ICI therapy. Collectively, targeting CD73 may provide new insights for tumor targeted therapy and/or immunotherapy.
Insights
High CD73 expression in head and neck squamous cell carcinoma (HNSCC) correlates with poor survival and resistance to immune checkpoint inhibitors (ICI). Targeting CD73 may improve immunotherapy outcomes for HNSCC patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Advanced head and neck squamous cell carcinoma (HNSCC) patients often have unsatisfactory responses to immune checkpoint inhibitors (ICI).
- CD73 is a potential immunotherapy target, but its role in HNSCC requires further investigation.
Purpose of the Study:
- To explore the function and prognostic significance of CD73 in HNSCC.
- To investigate the relationship between CD73 expression and the tumor immune microenvironment.
Main Methods:
- Analysis of TCGA-HNSC transcriptomic and clinical data.
- Immunohistochemistry to assess CD73 and CD8+ T cell expression.
- Bioinformatic analyses including GSEA, immune infiltration, single-cell RNA-seq, and mutation analysis.
Main Results:
- CD73 expression is significantly elevated in HNSCC tissues and associated with worse overall survival.
- High CD73 expression promotes epithelial-mesenchymal transition (EMT) and metastasis, and reduces CD8+ T cell infiltration.
- CD73-high tumors exhibit specific mutations (TP53, HRAS, CDKN2A), reduced TMB/MSI, and are linked to the APOBEC signature.
Conclusions:
- CD73 inhibits the tumor microenvironment and predicts unresponsiveness to ICI therapy in HNSCC.
- Targeting CD73 presents a potential strategy for novel tumor-targeted therapy and immunotherapy in HNSCC.
