Dynamic alterations of circulating T lymphocytes and the clinical response in patients with head and neck squamous cell carcinoma treated with nivolumab
Dynamic alterations of circulating T lymphocytes and the clinical response in patients with head and neck squamous cell carcinoma treated with nivolumab
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DOI：
10.1007/s00262-021-03042-y
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发表时间：
2021-08-31
影响因子：
5.8
通讯作者：
Chikamatsu, Kazuaki
中科院分区：
文献类型：
--
作者：
Tada, Hiroe;Takahashi, Hideyuki;Chikamatsu, Kazuaki
使用免疫检查点抑制剂（ICIs）的癌症免疫疗法已被认为是头颈鳞状细胞癌（HNSCC）的新型治疗选择。然而，只有大约 20-30% 的复发性/转移性 (R/M) HNSCC 患者受益。此外，ICIs 反应的潜在机制仍不清楚。我们使用流式细胞术和质量细胞术研究了接受纳武单抗治疗的 R/M HNSCC 患者循环 T 细胞亚群中免疫检查点分子的比例、激活状态和表达水平，然后确定治疗反应是否与这些值相关。我们还使用 IFN-gamma ELISPOT 测定评估了纳武单抗治疗前后肿瘤相关抗原、MAGE-A4 和 p53 特异性 T 细胞的频率变化。在疾病控制的患者中，活化的 CD4+ 和 CD8+ TEMRA 细胞的比例显着增加，但在疾病进展的患者中没有显着增加。正如预期的那样，无论治疗反应如何，T 细胞中 PD-1 的表达均显着下降。同时，治疗后疾病进展患者的 CD8+ T 细胞上 T 细胞免疫球蛋白 mucin-3 表达显着高于疾病控制患者。肿瘤相关抗原、MAGE-A4 和 p53 特异性 T 细胞的频率与临床反应不相关；然而，在疾病控制的患者中，MAGE-A4 特异性 T 细胞的频率显着增加。我们的结论是，在接受纳武单抗治疗的 R/M HNSCC 患者中，循环 T 细胞根据治疗效果表现出动态变化。因此，对循环 T 细胞免疫动力学的分析可以为 HNSCC 癌症免疫治疗的合理治疗策略提供新的见解。
Cancer immunotherapy using immune checkpoint inhibitors (ICIs) has been recognized as a novel therapeutic option for head and neck squamous cell carcinoma (HNSCC). However, only approximately 20-30% of patients with recurrent/metastatic (R/M) HNSCC benefit. Moreover, the mechanisms underlying the response to ICIs remain unclear. We investigated the proportion, activation status, and expression level of immune checkpoint molecules in circulating T cell subsets in R/M HNSCC patients treated with nivolumab using flow cytometry and mass cytometry, and then determined whether treatment response was associated with these values. We also assessed the changes in the frequency of tumor-associated antigens, MAGE-A4 and p53, -specific T cells prior to and after nivolumab treatment using the IFN-gamma ELISPOT assay. The proportion of activated CD4+ and CD8+ TEMRA cells significantly increased in the disease-controlled patients but not in disease-progressed patients. As expected, the expression of PD-1 in T cells markedly decreased regardless of the therapeutic response. Meanwhile, T cell immunoglobulin mucin-3 expression on CD8+ T cells was significantly higher in patients with disease progression than in disease-controlled patients after treatment. The frequency of the tumor-associated antigens, MAGE-A4- and p53-specific T cells, was not correlated with clinical responses; however, in the disease-controlled patients, the frequency of MAGE-A4-specific T cells was significantly augmented. We concluded that in R/M HNSCC patients treated with nivolumab, circulating T cells show dynamic alterations depending on treatment efficacy. An analysis of the immunokinetics of circulating T cells could thus provide new insights into rational therapeutic strategies in cancer immunotherapy for HNSCC.