关键词: Immunotherapy Non-small cell lung cancer (NSCLC) Prognosis Tertiary lymphoid structures (TLSs) Tumor microenvironment (TME)

Mesh : Humans Carcinoma, Non-Small-Cell Lung / immunology genetics pathology Tumor Microenvironment / immunology genetics Tertiary Lymphoid Structures / immunology pathology Lung Neoplasms / immunology genetics pathology mortality Prognosis Female Male Middle Aged Aged Immunotherapy / methods

来  源:   DOI:10.1038/s41598-024-64980-y   PDF(Pubmed)

Abstract:
Non-small cell lung cancer (NSCLC) is a common malignancy whose prognosis and treatment outcome are influenced by many factors. Some studies have found that tertiary lymphoid structures (TLSs) in cancer may contribute to prognosis and the prediction of immunotherapy efficacy However, the combined role of TLSs in NSCLC remains unclear. We accessed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to obtain mRNA sequencing data and clinical information as the TCGA cohort, and used our own sample of 53 advanced NSCLC as a study cohort. The samples were divided into TLS+ and TLS- groups by pathological tissue sections. Patients of the TLS+ group had a better OS (p = 0.022), PFS (p = 0.042), and DSS (p = 0.004) in the TCGA cohort, and the results were confirmed by the study cohort (PFS, p = 0.012). Furthermore, our result showed that the count and size of TLSs are closely associated with the efficacy of immunotherapy. In addition, the TLS+ group was associated with better immune status and lower tumor mutation load. In the tumor microenvironment (TME), the expression levels of CD4+ T cells and CD8+ T cells of different phenotypes were associated with TLSs. Overall, TLSs are a strong predictor of survival and immunotherapeutic efficacy in advanced NSCLC, and T cell-rich TLSs suggest a more ordered and active immune response site, which aids in the decision-making and application of immunotherapy in the clinic.
摘要:
非小细胞肺癌(NSCLC)是一种常见的恶性肿瘤,其预后和治疗效果受多种因素的影响。一些研究发现,三级淋巴结构(TLSs)可能有助于癌症的预后和预测免疫治疗的疗效。TLS在NSCLC中的联合作用尚不清楚.我们访问了癌症基因组图谱(TCGA)和基因表达综合(GEO)数据库,以获得mRNA测序数据和临床信息作为TCGA队列,并使用我们自己的53例晚期非小细胞肺癌样本作为研究队列。通过病理组织切片将样品分为TLS+和TLS-组。TLS+组的患者有较好的OS(p=0.022),PFS(p=0.042),和DSS(p=0.004)在TCGA队列中,结果得到了研究队列的证实(PFS,p=0.012)。此外,我们的结果表明,TLS的数量和大小与免疫治疗的疗效密切相关.此外,TLS+组具有较好的免疫状态和较低的肿瘤突变负荷.在肿瘤微环境(TME)中,不同表型的CD4+T细胞和CD8+T细胞的表达水平与TLSs相关。总的来说,TLSs是晚期非小细胞肺癌患者生存和免疫治疗疗效的强预测因子。富含T细胞的TLS表明了一个更有序和活跃的免疫反应位点,这有助于免疫治疗在临床中的决策和应用。
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