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Updated: Sep 11, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Single-Cell Transcriptomics Identifies Novel Prognostic Signatures in HNSCC Immunotherapy Response
Kankui Wu1, Xiuzhen Chen2, Qiaobin Wu3
1Department of Stomatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
Abstract:
Head and neck squamous cell carcinoma (HNSCC) poses a major therapeutic challenge. In this study, we aimed to analyze tumor immune microenvironment changes and develop a prognostic model based on immunotherapy response. We analyzed single-cell RNA sequencing data from three HNSCC patients receiving TLR8 agonist and anti-PD1 combination therapy, identified cell subpopulations before and after treatment with a focus on six major immune cell types, and developed a LASSO-Cox risk stratification model using combined single-cell and bulk RNA sequencing data. We identified 19 pre-treatment and 13 post-treatment cell subpopulations. Analysis of six major immune cell types revealed differential gene expression patterns. Based on treatment-induced differential genes, we developed a LASSO-Cox model with 51 survival-associated genes, which showed robust predictive performance (AUC: 0.749-0.800) across different timepoints for both HPV-positive and HPV-negative patients. High-risk groups had elevated MDSCs and CAFs, decreased immune cell infiltration (except Th2 CD4+ T cells and common lymphoid progenitors), and increased expression of ICB-related genes. In conclusion, our model effectively captures patients' immune status and provides insights for optimizing HNSCC immunotherapy strategies.
Insights
This study reveals how immunotherapy impacts the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC). A new model predicts patient outcomes based on immune cell changes, aiding treatment optimization.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Head and neck squamous cell carcinoma (HNSCC) presents significant therapeutic challenges.
- Understanding the tumor immune microenvironment is crucial for effective immunotherapy.
- Predictive models are needed to guide HNSCC treatment strategies.
Purpose of the Study:
- To analyze changes in the tumor immune microenvironment of HNSCC patients during immunotherapy.
- To develop a prognostic model for immunotherapy response in HNSCC.
- To identify immune cell signatures associated with treatment outcomes.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) data from HNSCC patients treated with TLR8 agonist and anti-PD1 therapy were analyzed.
- Cell subpopulations and immune cell types (six major types) were identified before and after treatment.
- A LASSO-Cox risk stratification model was developed using scRNA-seq and bulk RNA-seq data.
Main Results:
- 19 pre-treatment and 13 post-treatment cell subpopulations were identified.
- Differential gene expression patterns were observed in major immune cell types.
- A 51-gene LASSO-Cox model demonstrated robust predictive performance (AUC: 0.749-0.800) for patient survival.
- High-risk patients showed increased myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs), and altered immune cell infiltration.
Conclusions:
- The developed prognostic model effectively captures patient immune status in HNSCC.
- The model provides insights for optimizing immunotherapy strategies in HNSCC.
- Identifying immune cell signatures can improve treatment selection and patient outcomes.
