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Updated: May 21, 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 sequencing reveals tumor microenvironment features associated with the response to neoadjuvant
Pu-Gen An1,2,3, Wen-Jie Wu1,2,3, Xiao Hu1,2,3
1Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, No. 22 Zhongguancun South Avenue, Beijing, 100081, People's Republic of China.
Objectives:
In recent years, immune checkpoint inhibitors have shown promise as neoadjuvant therapies in the treatment of locally advanced oral squamous cell carcinoma (OSCC). However, the factors affecting the tumor response to immune checkpoint inhibitors (ICIs) remain unclear. This study aimed to analyze the impact of neoadjuvant chemoimmunotherapy (NACI) on the tumor microenvironment of OSCC via single-cell RNA sequencing, with the goal of optimizing treatment strategies.
Methods:
We analyzed biopsy, primary tumor, matched metastatic lymph node, and normal lymph node samples from four patients with OSCC receiving two cycles of tislelizumab (200 mg), albumin-bound paclitaxel (260 mg/m2), and cisplatin (60-75 mg/m2), with 3-week intervals between each cycle. This study explored the tumor microenvironment characteristics of tumors and metastatic lymph nodes in response to NACI.
Results:
We identified two major tumor cell subpopulations (C9 and C11), and patients with high expression of C11 subgroup-specific genes had a lower survival rate. FOXP3+ CD4 eTreg cells were found to potentially suppress the immune response. We found that NACI enhances antitumor immunity by promoting the proliferation of granzyme-expressing CD8+ T effector cells while simultaneously diminishing the effect of CD4+ T cells on Treg-mediated immune suppression. Furthermore, NACI was effective in suppressing inflammatory processes mediated by myeloid cells in tumors, contributing to its antitumor effects. The CCL19+ fibroblastic reticular cell (FRC) subgroup was significantly associated with the efficacy of NACI in patients with OSCC. We found that CCL19+ FRCs primarily exert their antitumor effects through interactions with CD8+ T lymphocytes via the -CXCL12‒CXCR4 axis.
Conclusion:
We explored the immune landscape of primary OSCC tumors and metastatic lymph nodes in relation to clinical response to NACI. Our findings offer valuable insights into patient treatment responses and highlight potential new therapeutic targets for the future management of OSCC.
Insights
Neoadjuvant chemoimmunotherapy (NACI) enhances antitumor immunity in oral squamous cell carcinoma (OSCC) by boosting CD8+ T cells and reducing immune suppression. This study reveals key immune microenvironment changes and potential therapeutic targets for OSCC treatment.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Immune checkpoint inhibitors (ICIs) show promise for neoadjuvant therapy in locally advanced oral squamous cell carcinoma (OSCC).
- Factors influencing tumor response to ICIs in OSCC are not fully understood.
- Optimizing neoadjuvant treatment strategies requires deeper insight into the tumor microenvironment's response.
Purpose of the Study:
- To analyze the impact of neoadjuvant chemoimmunotherapy (NACI) on the tumor microenvironment of OSCC using single-cell RNA sequencing.
- To identify key cellular and molecular changes induced by NACI in OSCC.
- To provide insights for optimizing NACI treatment strategies in OSCC.
Main Methods:
- Single-cell RNA sequencing of biopsy, primary tumor, and matched metastatic/normal lymph node samples from four OSCC patients.
- Patients received two cycles of tislelizumab, albumin-bound paclitaxel, and cisplatin.
- Exploration of tumor microenvironment characteristics in response to NACI.
Main Results:
- Identified two tumor cell subpopulations (C9, C11), with C11 high expression linked to lower survival.
- NACI enhanced antitumor immunity by promoting CD8+ T effector cell proliferation and reducing Treg-mediated suppression.
- NACI suppressed myeloid cell-mediated inflammation and identified CCL19+ fibroblastic reticular cells (FRCs) as key mediators of NACI efficacy via the CXCL12-CXCR4 axis with CD8+ T cells.
Conclusions:
- Explored the immune landscape of primary OSCC tumors and metastatic lymph nodes in relation to clinical response to NACI.
- Findings provide valuable insights into patient treatment responses to NACI.
- Highlighted potential new therapeutic targets for future OSCC management.
