PD-L1及肿瘤免疫微环境对预测口腔鳞癌新辅助治疗效果的意义

doi:10.19438/j.cjoms.2023.06.007

摘要/Abstract

摘要： 目的: 探索程序性死亡配体1（programmed cell death-ligand 1,PD-L1）表达及肿瘤免疫微环境对评估口腔鳞癌新辅助免疫治疗联合化疗疗效的临床意义。方法: 回顾分析2019年8月—12月于解放军总医院第一医学中心口腔外科使用新辅助治疗的20例口腔鳞癌患者的临床资料。使用免疫组织化学染色法检测口腔鳞癌PD-L1的表达情况;采用多重荧光免疫组织化学染色(mIHC)检测口腔鳞癌免疫微环境中CD8⁺ T淋巴细胞、CD68⁺巨噬细胞、PD-1⁺细胞、CD8⁺PD-1⁺ T淋巴细胞、CD68⁺PD-L1⁺巨噬细胞的表达水平。采用SPSS 21.0软件包对数据进行统计学分析。结果: 口腔鳞癌PD-L1阳性表达在肿瘤比例评分（TPS）≥1%、综合阳性评分（CPS）≥1标准下的表达率分别为65%和85%,PD-L1高表达（CPS≥20）占比50%;PD-L1表达与年龄、性别、肿瘤分化、颈淋巴结转移无明显相关（P>0.05）。新辅助治疗2个周期临床应答率为55%,生存分析显示,PD-L1阳性表达组的无进展生存期（PFS）及无瘤生存期（DFS）显著高于PD-L1阴性表达组（P<0.05）。口腔鳞癌PD-L1表达与CD68⁺PD-L1⁺巨噬细胞占比大于50%呈正相关,PD-L1阳性表达且CD68⁺PD-L1⁺巨噬细胞占比高于50%的患者新辅助治疗后临床应答率为70%。结论: 新辅助免疫治疗联合化疗有可能进一步延长PD-L1表达阳性口腔鳞癌患者的无瘤生存期,CD68⁺PD-L1⁺巨噬细胞高表达对评估口腔鳞癌新辅助治疗疗效具有重要临床意义。

关键词: 口腔鳞癌, 新辅助免疫治疗, 化疗, PD-1/PD-L1, 肿瘤免疫微环境

Abstract: PURPOSE: To explore the clinical significance of the expression of programmed cell death-ligand 1(PD-L1) and tumor immune microenvironment for the evaluation of the efficacy of neoadjuvant immunotherapy combined with chemotherapy in oral squamous cell carcinoma(OSCC). METHODS: The clinical data of 20 patients with OSCC who received neoadjuvant therapy in the Department of Oral Surgery of the First Medical Center of PLA General Hospital from August to December 2019 were retrospectively analyzed. The expression of PD-L1 in OSCC was detected by immunohistochemical staining. The expression levels of CD8⁺ T lymphocytes, CD68⁺ macrophages, PD-1⁺ cells, CD8⁺PD-1⁺ T lymphocytes and CD68⁺PD-L1⁺ macrophages in the immune microenvironment of OSCC were detected by multiple fluorescent immunohistochemical staining (mIHC). SPSS 21.0 software package was used for data analysis. RESULTS: The positive expression rates of PD-L1 in OSCC were 65% and 85% under the criteria of tumor proportion score(TPS)≥1% and combined positive score(CPS)≥1, respectively, and the high expression of PD-L1 (CPS≥20) accounted for 50%. There was no significant correlation between PD-L1 expression and age, sex, tumor differentiation and cervical lymph node metastasis (P>0.05). The clinical response rate after 2 cycles of neoadjuvant therapy was 55%. Survival analysis showed that the progression-free survival(PFS) and disease-free survival(DFS) of PD-L1 positive expression group were significantly higher than those of PD-L1 negative expression group (P<0.05). The expression of PD-L1 in OSCC was positively correlated with CD68⁺PD-L1⁺macrophages accounting for more than 50%, and the clinical response rate of patients with positive expression of PD-L1 and CD68⁺PD-L1⁺ macrophages accounting for more than 50% was 70% after neoadjuvant therapy. CONCLUSIONS: Neoadjuvant immunotherapy combined with chemotherapy may further prolong the DFS of patients with OSCC with positive expression of PD-L1. The high expression of CD68⁺PD-L1⁺ macrophage has important clinical significance for evaluating the efficacy of neoadjuvant therapy for OSCC.

Key words: Oral squamous cell carcinoma, OSCC, Neoadjuvant Immunotherapy, Chemotherapy, PD-1/PD-L1, Tumor immune microenvironment

中图分类号:

R739.8

靳能皓, 田瑜, 朱亮, 乔波, 李粮博, 张海钟, 张蕾. PD-L1及肿瘤免疫微环境对预测口腔鳞癌新辅助治疗效果的意义[J]. 中国口腔颌面外科杂志, 2023, 21(6): 572-578.

JIN Neng-hao, TIAN Yu, ZHU Liang, QIAO Bo, LI Liang-bo, ZHANG Hai-zhong, ZHANG Lei. Clinical significance of PD-L1 and tumor immune microenvironment in predicting neoadjuvant therapy for oral squamous cell carcinoma[J]. China J Oral Maxillofac Surg, 2023, 21(6): 572-578.

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