Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer, with limited responsiveness to immune checkpoint inhibitors (ICIs). Cancer vaccine therapy is a promising novel immunotherapeutic approach that stimulates tumor-specific T cells. Receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is overexpressed in malignant tumors but minimally expressed in normal tissues, presents a promising target for immunotherapy. This study aimed to evaluate ROR1 as a target for helper T lymphocyte (HTL)-based peptide vaccine immunotherapy in HNSCC.Methods: ROR1 expression in HNSCC tissues was assessed by immunohistochemistry. A novel ROR1-derived epitope (ROR1403–417) was identified and used to generate ROR1-reactive HTLs. Functional assays measuring IFN-γ and granzyme B secretion, as well as direct cytotoxicity, were performed. The effects of ICIs on HTL activity were also examined. The presence of ROR1-reactive T cells in the peripheral blood of patients with HNSCC was evaluated.Results: ROR1 positivity rates in HNSCC tissues were significantly higher (80.0%) than those in healthy controls (16.7%), and high ROR1 expression correlated with advanced clinical stages. HTL lines recognized the ROR1403–417peptide in a human leukocyte antigen (HLA)-DR-restricted manner, secreted effector cytokines, and exhibited direct cytotoxicity against ROR1+ tumor cells. Dual PD-L1/PD-L2 blockade further enhanced HTL responses. ROR1-reactive T cells were detected in the peripheral blood of patients with HNSCC.Conclusions: ROR1 represents a promising target for immunotherapy in HNSCC. The ROR1403–417peptide can elicit ROR1-reactive HTLs that exhibit antitumor responses against HNSCC cell lines, which can be enhanced by ICIs. These findings support the potential of ROR1-targeted peptide vaccine therapy for HNSCC.
背景/目的：头颈部鳞状细胞癌（HNSCC）是第七大常见癌症，对免疫检查点抑制剂（ICIs）的反应有限。癌症疫苗疗法是一种有前景的新型免疫治疗策略，可刺激肿瘤特异性T细胞。受体酪氨酸激酶样孤儿受体1（ROR1）在恶性肿瘤中过表达，但在正常组织中表达极低，是免疫治疗的潜在靶点。本研究旨在评估ROR1作为基于辅助T淋巴细胞（HTL）的肽疫苗免疫治疗在HNSCC中的靶点价值。 方法：通过免疫组织化学检测HNSCC组织中ROR1的表达。鉴定出一种新型ROR1衍生表位（ROR1403–417），并用于诱导ROR1反应性HTLs。通过检测IFN-γ和颗粒酶B的分泌以及直接细胞毒性进行功能分析。同时考察了ICIs对HTL活性的影响。评估了HNSCC患者外周血中ROR1反应性T细胞的存在情况。 结果：HNSCC组织中ROR1阳性率（80.0%）显著高于健康对照组（16.7%），且ROR1高表达与晚期临床分期相关。HTL细胞系以人类白细胞抗原（HLA）-DR限制性方式识别ROR1403–417肽段，分泌效应细胞因子，并对ROR1阳性肿瘤细胞表现出直接细胞毒性。双重PD-L1/PD-L2阻断进一步增强了HTL反应。在HNSCC患者外周血中检测到了ROR1反应性T细胞。 结论：ROR1是HNSCC免疫治疗的一个有前景的靶点。ROR1403–417肽段能够诱导出对HNSCC细胞系具有抗肿瘤反应的ROR1反应性HTLs，且该反应可被ICIs增强。这些发现支持了ROR1靶向肽疫苗疗法在HNSCC中的治疗潜力。
肿瘤(癌症)患者之家