CD161+CD127+CD8+ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus

• Published in: Oncoimmunology 2024-12, Vol.13 (1), p.2371575
• Main Authors: Qu, Jingjing, Li, Yuekang, Wu, Binggen, Shen, Qian, Chen, Lijun, Sun, Wenjia, Wang, Bo, Ying, Lixiong, Wu, Li, Zhou, Hong, Zhou, Jianya, Zhou, Jianying
• Format: Article
• Language: English
• Subjects: Adult; Aged; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - immunology; CD127; CD161; CD161+CD127+CD8+ T cells; CD8; CD8-Positive T-Lymphocytes - immunology; diabetes mellitus; Diabetes Mellitus - drug therapy; Diabetes Mellitus - immunology; Female; Humans; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; immunotherapy; Immunotherapy - methods; Interleukin-7 Receptor alpha Subunit - metabolism; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Male; Middle Aged; non-small cell lung cancer; Original Research; predictive biomarkers; Prognosis; Programmed Cell Death 1 Receptor - antagonists & inhibitors; T cells; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 2162-402X; 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2024.2371575

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.