Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Eur J Cancer. 2022 Oct;174:10-20. doi: 10.1016/j.ejca.2022.07.004. Epub 2022 Aug 12.
T-cell factor 1 (TCF1)Programmed cell death-1 (PD-1) tumour-infiltrating lymphocytes (TILs) are a recently defined subset of exhausted T-cells (Texh-cells) that exhibit a progenitor phenotype. They have been associated with a response to immune checkpoint inhibitor (ICI) therapy in murine tumour models and in patients with malignant melanoma. We investigated the significance of TCF1PD-1 TILs as a predictive biomarker for ICI therapy response in non-small-cell lung cancer (NSCLC).
Two different cohorts of NSCLC patients treated with ICI targeting the PD-1/PD-L1 pathway were included. RNA-seq was performed using NSCLC tissues obtained from 234 patients prior to immunotherapy (RNA-seq cohort). Double immunostaining of TCF1 and PD-1 and single immunostaining of other immunologic markers were performed in resected tumour tissues from another 116 patients (immunohistochemistry cohort).
In the RNA-seq cohort, both Texh-cell and progenitor Texh-cell gene sets were enriched in responders compared with non-responders. Larger Texh-cell fractions and increased progenitor Texh-cell gene sets were significantly associated with better progression-free survival (PFS). In the immunohistochemistry cohort, the TCF1PD-1 TIL number and PD-L1 tumour proportion score were significantly higher in responders than in non-responders. A high number of TCF1PD-1 TILs was significantly associated with both PFS and overall survival (OS) after ICI therapy, and it independently predicted a better PFS and OS according to multivariate analysis.
TCF1PD-1 TILs, representing progenitor Texh-cells, predict both better response and survival in NSCLC patients after ICI therapy. Thus, they may be a useful predictive biomarker for ICI therapy in NSCLC.
T 细胞因子 1（TCF1）程序性细胞死亡-1（PD-1）肿瘤浸润淋巴细胞（TILs）是最近定义的衰竭 T 细胞（Texh 细胞）亚群，表现出祖细胞表型。它们与鼠肿瘤模型和恶性黑色素瘤患者对免疫检查点抑制剂（ICI）治疗的反应有关。我们研究了 TCF1PD-1 TILs 作为非小细胞肺癌（NSCLC）ICI 治疗反应的预测生物标志物的意义。
纳入了接受针对 PD-1/PD-L1 通路的 ICI 治疗的两个不同队列的 NSCLC 患者。对 234 名接受免疫治疗前的 NSCLC 患者的组织进行了 RNA-seq（RNA-seq 队列）。对另 116 名接受手术切除的肿瘤组织进行了 TCF1 和 PD-1 的双重免疫染色和其他免疫标志物的单一免疫染色（免疫组化队列）。
在 RNA-seq 队列中，与无反应者相比，反应者中 Texh 细胞和祖细胞 Texh 细胞基因集均富集。较大的 Texh 细胞分数和增加的祖细胞 Texh 细胞基因集与更好的无进展生存期（PFS）显著相关。在免疫组化队列中，与无反应者相比，反应者中的 TCF1PD-1 TIL 数量和 PD-L1 肿瘤比例评分显著更高。高数量的 TCF1PD-1 TIL 与 ICI 治疗后的 PFS 和总生存期（OS）均显著相关，并且根据多变量分析独立预测了更好的 PFS 和 OS。
TCF1PD-1 TILs 代表祖细胞 Texh 细胞，可预测 NSCLC 患者接受 ICI 治疗后的反应和生存情况。因此，它们可能是 NSCLC 中 ICI 治疗的有用预测生物标志物。
