An Pu-Gen, Wu Wen-Jie, Hu Xiao, Zhang Zi-Qi, Zhang Jie
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, No. 22 Zhongguancun South Avenue, Beijing, 100081, People's Republic of China.
National Center of Stomatology and National Clinical Research Center for Oral Diseases, Beijing, People's Republic of China.
Cancer Immunol Immunother. 2025 Mar 19;74(5):151. doi: 10.1007/s00262-025-04014-2.
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.
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/m), and cisplatin (60-75 mg/m), with 3-week intervals between each cycle. This study explored the tumor microenvironment characteristics of tumors and metastatic lymph nodes in response to NACI.
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.
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.
近年来，免疫检查点抑制剂在局部晚期口腔鳞状细胞癌（OSCC）治疗中作为新辅助治疗显示出前景。然而，影响肿瘤对免疫检查点抑制剂（ICI）反应的因素仍不清楚。本研究旨在通过单细胞RNA测序分析新辅助化疗免疫疗法（NACI）对OSCC肿瘤微环境的影响，以优化治疗策略。
我们分析了4例接受两个周期替雷利珠单抗（200mg）、白蛋白结合型紫杉醇（260mg/m²）和顺铂（60 - 75mg/m²）治疗的OSCC患者的活检组织、原发性肿瘤、配对的转移淋巴结和正常淋巴结样本，每个周期间隔3周。本研究探讨了肿瘤和转移淋巴结对NACI反应的肿瘤微环境特征。
我们鉴定出两个主要的肿瘤细胞亚群（C9和C11），C11亚群特异性基因高表达的患者生存率较低。发现FOXP3⁺ CD4⁺ eTreg细胞可能抑制免疫反应。我们发现NACI通过促进表达颗粒酶的CD8⁺ T效应细胞增殖来增强抗肿瘤免疫力，同时减弱CD4⁺ T细胞对Treg介导的免疫抑制的影响。此外，NACI可有效抑制肿瘤中髓样细胞介导的炎症过程，从而发挥其抗肿瘤作用。CCL19⁺成纤维网状细胞（FRC）亚群与OSCC患者NACI的疗效显著相关。我们发现CCL19⁺ FRCs主要通过-CXCL12-CXCR4轴与CD8⁺ T淋巴细胞相互作用发挥其抗肿瘤作用。
我们探讨了原发性OSCC肿瘤和转移淋巴结与NACI临床反应相关的免疫格局。我们的研究结果为患者治疗反应提供了有价值的见解，并突出了OSCC未来管理的潜在新治疗靶点。
