TCR Repertoire profiling in tumor tissue, malignant pleural effusion and peripheral blood of elderly non-small cell lung cancer patients
10.3760/cma.j.issn.0254-9026.2025.07.012
- VernacularTitle:老年非小细胞肺癌肿瘤组织、恶性胸腔积液与外周血T细胞受体免疫组库图谱
- Author:
Qin TAN
1
;
Jie MA
1
Author Information
1. 北京医院 生物治疗中心 国家老年医学中心 中国医学科学院老年医学研究院，北京 100730
- Publication Type:Journal Article
- Keywords:
Carcinoma, non-small-cell lung;
Pleural effusion, malignant;
Genes, T-cell receptor;
Diversity;
Shared clonotype
- From:
Chinese Journal of Geriatrics
2025;44(7):917-924
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To compare the T cell receptor(TCR)repertoires of tumor tissue, malignant pleural effusion(MPE), and peripheral blood in elderly patients with non-small cell lung cancer(NSCLC), and to explore MPE as a potential source of tumor-specific T cells for adoptive cell therapy.Methods:Matched tumor biopsies, MPE, and peripheral blood samples were collected from five advantaged-stage NSCLC elderly patients with MPE, who were treated at Beijing hospital during August 2022 to June 2023.All 5 cases were male, aged 60-78 years, with a median age of 68 years.Genomic DNA was extracted, and TCR β-chain genes were subjected to high-throughput sequencing using the Illumina HiSeq6000 platform.Repertoire metrics, including clonotype distribution, diversity, and shared TCR clones, were analyzed.Results:The heterogeneity of complementarity determining region 3(CDR3)length distribution and clonotype frequency profiles was observed across tumor tissue, MPE, and blood.Furthermore, MPE exhibited significantly elevated TCR diversity compared to tumor tissue and blood, as quantified by Shannon entropy analysis( P<0.05).Notably, MPE demonstrated an increase in shared CDR3 clonotypes and a higher overlap value with tumor tissue than that observed in blood-tumor pairs( P<0.05).Multi-modal joint clustering analysis(phylogenetic analysis)delineated co-clustering patterns between MPE and tumor-derived TCR repertoires, while peripheral blood clonotypes formed a separate phylogenetic branch.Additionally, the frequency of shared TCR clonotypes between MPE and tumor significantly exceeded that of blood-tumor pairs( P<0.05). Conclusions:MPE exhibits greater TCR diversity compared to tumor tissue and peripheral blood, while its clonal architecture shows a preferential overlap with tumor-derived TCR repertoires.This suggests that tumor-specific T cells in MPE may possess enhanced clonal expansion dynamics relative to those in peripheral blood.
