Clinical significance of peripheral TCR and BCR repertoire diversity in EGFR/ALK wild-type NSCLC treated with anti-PD-1 antibody
Clinical significance of peripheral TCR and BCR repertoire diversity in EGFR/ALK wild-type NSCLC treated with anti-PD-1 antibody
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DOI：
10.1007/s00262-021-02900-z
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发表时间：
2021-03-09
影响因子：
5.8
通讯作者：
Sasada, Tetsuro
中科院分区：
文献类型：
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作者：
Nakahara, Yoshiro;Matsutani, Takaji;Sasada, Tetsuro
引言TCR和BCR库的多样性在肿瘤免疫中起着关键作用。因此，TCR和BCR库的分析可能有助于预测抗PD-1治疗的临床疗效。方法收集30例经抗PD-1抗体治疗的非小细胞肺癌（NSCLC）患者治疗前及治疗后6周的外周血标本。在所有入组患者（n = 30）或EGFR/ALK突变患者（n = 10）或无EGFR/ALK突变患者（n = 20）中，评价外周血TCR和BCR库多样性的临床意义。结果TCR和BCR多样性在基线（R = 0.65; P = 1.6 x 10（-4））和治疗（R = 0.72; P = 1.2 x 10（-5））时显著相关。与无应答者（SD或PD）相比，EGFR/ALK野生型亚组中的应答者（PR）在治疗后显示TCR和BCR多样性显著降低（分别为P = 0.0014和P = 0.034），但并非所有入组患者均如此。治疗后TCR和BCR谱系多样性的减少也与EGFR/ALK野生型子集中不良事件的发生显着相关（分别为P = 0.022和P = 0.014）。TCR多样性降低的患者在EGFR/ALK野生型亚组中显示出更好的无进展生存期（PFS）（P = 0.011），但在突变亚组中则不然。结论EGFR/ALK突变阴性的NSCLC患者抗PD-1治疗后外周血TCR和BCR谱多样性的变化具有临床意义。监测外周TCR和BCR库可作为早期检测EGFR/ALK野生型NSCLC患者的替代标志物，这些患者将从抗PD-1治疗中获益。
Introduction TCR and BCR repertoire diversity plays a critical role in tumor immunity. Thus, analysis of TCR and BCR repertoires might help predict the clinical efficacy of anti-PD-1 treatment. Methods Blood samples from 30 patients with non-small cell lung cancer (NSCLC) treated with anti-PD-1 antibody were collected before and six weeks after treatment initiation. The clinical significance of TCR and BCR repertoire diversity in peripheral blood was evaluated in all the enrolled patients (n = 30) or in the subset with (n = 10) or without (n = 20) EGFR/ALK mutation. Results TCR and BCR diversity was significantly correlated at baseline (R = 0.65; P = 1.6 x 10(-4)) and on treatment (R = 0.72; P = 1.2 x 10(-5)). Compared to non-responders (SD or PD), responders (PR) showed significantly decreased TCR and BCR diversity after treatment in the EGFR/ALK wild-type subset (P = 0.0014 and P = 0.034, respectively), but not in all the enrolled patients. The post-treatment reduction in TCR and BCR repertoire diversity was also significantly associated with the occurrence of adverse events in the EGFR/ALK wild-type subset (P = 0.022 and P = 0.014, respectively). Patients with more reduced TCR diversity showed better progression-free survival (PFS) in the EGFR/ALK wild-type subset (P = 0.011) but not in the mutant subset. Conclusions These findings suggest the clinical significance of changes in peripheral TCR and BCR repertoire diversity after anti-PD-1 treatment in patients with NSCLC without EGFR/ALK mutation. Monitoring of the peripheral TCR and BCR repertoires may serve as a surrogate marker for the early detection of EGFR/ALK wild-type NSCLC patients who would benefit from anti-PD-1 treatment.