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Updated: Jun 27, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Characterization of macrophages in head and neck squamous cell carcinoma and development of MRG-based risk signature
1Department of Otorhinolaryngology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China.
Abstract:
Macrophages are immune cells in the TME that can not only inhibit angiogenesis, extracellular matrix remodeling, cancer cell proliferation, and metastasis but also mediate the phagocytosis and killing of cancer cells after activation, making them key targets in anti-tumor immunotherapy. However, there is little research on macrophages and their relation to disease prognosis in HNSCC. Initially, we collected scRNA-seq, bulk RNA-seq, and clinical data. Subsequently, we identified macrophages and distinguished MRGs. Using the K-means algorithm, we performed consensus unsupervised clustering. Next, we used ssGSEA analysis to assess immune cell infiltration in MRG clusters. A risk model was established using multivariate Cox analysis. Then, Kaplan-Meier, ROC curves, univariate and multivariate COX analyses, and C-index was used to validate the predictive power of the signature. The TIDE method was applied to assess the response to immunotherapy in patients diagnosed with HNSCC. In addition, drug susceptibility predictions were made for the GDSC database using the calcPhenotype function. We found that 8 MRGs had prognostic potential. Patients in the MRG group A had a higher probability of survival, and MRG clusters A and B had different characteristics. Cluster A had a higher degree of expression and infiltration in MRG, indicating a closer relationship with MRG. The accuracy of the signature was validated using univariate and multivariate Cox analysis, C-index, and nomogram. Immune landscape analysis found that various immune functions were highly expressed in the low-risk group, indicating an improved response to immunotherapy. Finally, drugs with high sensitivity to HNSCC (such as 5-Fluorouracil, Temozolomide, Carmustine, and EPZ5676) were explored and analyze the malignant characteristics of HNSCC. We constructed a prognostic model using multivariate Cox analysis, consisting of 8 MRGs (TGM2, STC1, SH2D3C, PIK3R3, MAP3K8, ITGA5, ARHGAP4, and AQP1). Patients in the low-risk group may have a higher response to immunotherapy. The more prominent drugs for drug selection are 5-fluorouracil, temozolomide and so on. Malignant features associated with HNSCC include angiogenesis, EMT, and the cell cycle. This study has opened up new prospects for the prognosis, prediction, and clinical treatment strategy of HNSCC.
Insights
This study identifies 8 macrophage-related genes (MRGs) that predict survival in head and neck squamous cell carcinoma (HNSCC). A prognostic model suggests patients in the low-risk group may respond better to immunotherapy and specific drugs.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Macrophages are crucial immune cells within the tumor microenvironment (TME), influencing cancer progression and immunotherapy response.
- Limited research exists on macrophage roles and prognostic significance in head and neck squamous cell carcinoma (HNSCC).
Purpose of the Study:
- To identify macrophage-related genes (MRGs) and develop a prognostic signature for HNSCC.
- To investigate the relationship between MRGs, immune infiltration, and immunotherapy response in HNSCC patients.
Main Methods:
- Collected and analyzed single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing, and clinical data for HNSCC.
- Utilized K-means clustering, ssGSEA, and multivariate Cox analysis to identify MRGs and construct a prognostic model.
- Validated the signature's predictive power using Kaplan-Meier curves, ROC analysis, and C-index; assessed immunotherapy response via TIDE.
Main Results:
- Identified 8 MRGs (TGM2, STC1, SH2D3C, PIK3R3, MAP3K8, ITGA5, ARHGAP4, AQP1) with prognostic potential in HNSCC.
- Developed a validated prognostic signature; patients in the low-risk group exhibited higher survival probability and enhanced immune function.
- The low-risk group showed potential for improved immunotherapy response, with identified sensitive drugs including 5-Fluorouracil and Temozolomide.
Conclusions:
- The developed 8-MRG prognostic model accurately predicts survival and immunotherapy response in HNSCC.
- This signature offers valuable insights for personalized treatment strategies and clinical decision-making in HNSCC.
- Identified potential therapeutic targets and drugs, including 5-Fluorouracil and Temozolomide, for HNSCC treatment.
