CD161 CD127 CD8 T 细胞在患有糖尿病的非小细胞肺癌 (NSCLC) 患者中的作用仍有待探索。本研究确定了患有糖尿病的 NSCLC 中 CD8 T 细胞亚群的患病率、表型和功能。我们招募了接受抗 PD-1 免疫疗法作为一线治疗的 NSCLC 患者 (n = 436)。分析伴或不伴糖尿病的 NSCLC 患者的无进展生存期 (PFS)、总生存期 (OS)、T 细胞浸润和外周血免疫学特征。患有糖尿病的 NSCLC 患者表现出较短的 PFS 和 OS（分别为 p = 0.0069 和 p = 0.012），并且 CD8 T 细胞浸润显着降低。飞行时间质谱流式细胞仪 (CyTOF) 显示，抗 PD-1 治疗前患有糖尿病的 NSCLC 中 CD161 CD127 CD8 T 细胞的比例高于非糖尿病 NSCLC (p = 0.0071)，并且这一趋势抗 PD-1 治疗后继续治疗 (p = 0.0393)。流式细胞术和多重免疫荧光证实，合并糖尿病的 NSCLC 患者的 CD161 CD127 CD8 T 细胞与 CD8 T 细胞的比率显着高于非糖尿病 NSCLC 患者。 RNA测序分析显示，与糖尿病NSCLC中的CD161 CD127-CD8 T细胞相比，CD161 CD127 CD8 T细胞亚群中的免疫细胞毒性基因减少。 CD161 CD127 CD8 T 细胞在患有糖尿病的 NSCLC 中表现出更多的 T 细胞耗尽表型。 CD161 CD127 CD8 T 细胞与 CD8 T 细胞比率≥6.3% 的患有糖尿病的 NSCLC 患者表现出较差的 PFS。这些发现表明，糖尿病是接受抗PD-1免疫治疗的NSCLC患者的危险因素。CD161 CD127 CD8 T细胞可能是伴有糖尿病的NSCLC患者预后不良的关键指标。我们的研究结果将有助于推进非小细胞肺癌糖尿病患者的抗 PD-1 治疗。© 2024 作者。由泰勒授权出版

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127-CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.