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Abstract：
Herein, we characterize the landscape and prognostic significance of the T cell receptor (TCR) repertoire of early-stage non-small cell lung cancer (NSCLC) for patients with an epidermal growth factor receptor (EGFR) mutation. β Chain TCR sequencing was used to characterize the TCR repertoires of paraffin-preserved pretreatment tumor and tumor-adjacent tissues from 57 and 44 patients with stage II/III NSCLC with an EGFR mutation treated with gefitinib or chemotherapy in the ADJUVANT-CTONG 1104 trial. The TCR diversity was significantly decreased in patients with an EGFR mutation, and patients with high TCR diversity had a favorable overall survival (OS). A total of 10 TCR Vβ-Jβ rearrangements were significantly associated with OS. Patients with a higher frequency of Vβ5-6Jβ2-1, Vβ20-1Jβ2-1, Vβ24-1Jβ2-1, and Vβ29-1Jβ2-7 had significantly longer OS. Weighted combinations of the 4 TCRs were significantly associated with OS and disease-free survival (DFS) of patients, which could further stratify the high and low TCR diversity groups. Importantly, Vβ5-6Jβ2-1, Vβ20-1Jβ2-1, and Vβ24-1Jβ2-1 had a significant relationship with gefitinib treatment, while Vβ29-1Jβ2-7 was associated with chemotherapy. Four TCR Vβ-Jβ rearrangements related to favorable OS and DFS for adjuvant gefitinib and chemotherapy in patients with an EGFR mutation with stage II/III NSCLC; this may provide a novel perspective for the adjuvant setting for resectable NSCLC.
摘要：
在这里，我们描述了表皮生长因子受体(EGFR)突变患者早期非小细胞肺癌(NSCLC)T细胞受体(TCR)谱的前景和预后意义.在ADJUVANT-CTONG1104试验中，使用β链TCR测序来表征57和44例II/III期NSCLC患者的石蜡保存的预处理肿瘤和肿瘤旁组织的TCR库，这些患者接受吉非替尼或化疗。EGFR突变患者的TCR多样性显著降低,TCR多样性高的患者具有良好的总生存期（OS）。共有10例TCRVβ-Jβ重排与OS显著相关。Vβ5-6Jβ2-1，Vβ20-1Jβ2-1，Vβ24-1Jβ2-1和Vβ29-1Jβ2-7频率较高的患者的OS明显更长。4种TCR的加权组合与患者的OS和无病生存期（DFS）显着相关，这可以进一步分层高和低TCR多样性组。重要的是,Vβ5-6Jβ2-1、Vβ20-1Jβ2-1和Vβ24-1Jβ2-1与吉非替尼治疗有显著关系,而Vβ29-1Jβ2-7与化疗有关。在EGFR突变的II/III期NSCLC患者中，四种TCRVβ-Jβ重排与吉非替尼和化疗的有利OS和DFS相关；这可能为可切除NSCLC的辅助设置提供新的视角。
