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循环 CD137 T 细胞水平与晚期头颈部癌症患者对派姆单抗治疗的反应相关。

Circulating CD137 T Cell Levels Are Correlated with Response to Pembrolizumab Treatment in Advanced Head and Neck Cancer Patients.

机构信息

Division of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, "Sapienza" University of Rome, 00161 Rome, Italy.

Laboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.

出版信息

Int J Mol Sci. 2023 Apr 12;24(8):7114. doi: 10.3390/ijms24087114.

Abstract

Pembrolizumab, an anti-PD-1 antibody, has been approved as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma ((R/M) HNSCC). However, only a minority of patients benefit from immunotherapy, which highlights the need to identify novel biomarkers to optimize treatment strategies. CD137 T cells have been identified as tumour-specific T cells correlated with immunotherapy responses in several solid tumours. In this study, we investigated the role of circulating CD137 T cells in (R/M) HNSCC patients undergoing pembrolizumab treatment. PBMCs obtained from 40 (R/M) HNSCC patients with a PD-L1 combined positive score (CPS) ≥1 were analysed at baseline via cytofluorimetry for the expression of CD137, and it was found that the percentage of CD3CD137 cells is correlated with the clinical benefit rate (CBR), PFS, and OS. The results show that levels of circulating CD137 T cells are significantly higher in responder patients than in non-responders ( = 0.03). Moreover, patients with CD3CD137 percentage ≥1.65% had prolonged OS ( = 0.02) and PFS ( = 0.02). Multivariate analysis, on a combination of biological and clinical parameters, showed that high levels of CD3CD137 cells (≥1.65%) and performance status (PS) = 0 are independent prognostic factors of PFS (CD137 T cells, = 0.007; PS, = 0.002) and OS (CD137 T cells, = 0.006; PS, = 0.001). Our results suggest that levels of circulating CD137 T cells could serve as biomarkers for predicting the response of (R/M) HNSCC patients to pembrolizumab treatment, thus contributing to the success of anti-cancer treatment.

摘要

帕博利珠单抗是一种抗 PD-1 抗体,已被批准用于复发性或转移性头颈部鳞状细胞癌((R/M)HNSCC)的一线治疗。然而,只有少数患者从免疫治疗中获益,这凸显了需要确定新的生物标志物来优化治疗策略。在几种实体瘤中,CD137 T 细胞已被确定为与免疫治疗反应相关的肿瘤特异性 T 细胞。在这项研究中,我们研究了循环 CD137 T 细胞在接受帕博利珠单抗治疗的(R/M)HNSCC 患者中的作用。通过细胞荧光法分析了 40 名(R/M)HNSCC 患者的 PBMCs,这些患者的 PD-L1 联合阳性评分(CPS)≥1,发现在基线时,CD3CD137 细胞的百分比与临床获益率(CBR)、无进展生存期(PFS)和总生存期(OS)相关。结果表明,应答患者的循环 CD137 T 细胞水平明显高于无应答者( = 0.03)。此外,CD3CD137 百分比≥1.65%的患者具有更长的 OS( = 0.02)和 PFS( = 0.02)。基于生物和临床参数的组合的多变量分析表明,高水平的 CD3CD137 细胞(≥1.65%)和表现状态(PS)=0 是 PFS(CD137 T 细胞, = 0.007;PS, = 0.002)和 OS(CD137 T 细胞, = 0.006;PS, = 0.001)的独立预后因素。我们的结果表明,循环 CD137 T 细胞水平可作为预测(R/M)HNSCC 患者对帕博利珠单抗治疗反应的生物标志物,从而有助于抗癌治疗的成功。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0200/10138766/e00b178b26e8/ijms-24-07114-g001.jpg

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