
화학요법은 폐선암 종양 세포, 면역 세포, 간질 세포의 대사 재프로그래밍을 유도하여 종양 미세환경을 크게 변화시킨다. 이는 화학요법 효과와 내성 기전을 이해하는 데 중요한 통찰을 제공한다.


coremsg

Neoadjuvant chemotherapy has emerged as a significant therapeutic approach in the management of lung cancer, aiming to improve outcomes through preoperative systemic treatment. However, the mechanisms underlying treatment efficacy and resistance remain largely unknown. In this study, scRNA-seq analysis of tumor samples from nine lung adenocarcinoma (LUAD) patients, including four with surgery alone and five with neoadjuvant chemotherapy, was conducted. Additionally, a series of in vitro and in vivo assays, encompassing flow cytometry, immunofluorescence, seahorse assay, and tumor xenograft models, were employed to validate our findings. A total of 83,622 cells were analyzed, revealing high heterogeneity in cell type composition across different groups. Functional enrichment analysis uncovered significant metabolic reprogramming induced by chemotherapy in both tumor cells and macrophages. Notably, two macrophage subtypes were identified: Anti-mac cells (CD45+CD11b+CD86+) and Pro-mac cells (CD45+CD11b+ARG+), with the proportion of Pro-mac cells significantly increasing in LUAD tissues after neoadjuvant chemotherapy. Pro-mac cells were found to promote tumor growth and angiogenesis while suppressing tumor immunity. Furthermore, analysis of T and B cell remodeling induced by neoadjuvant therapy revealed a more robust immune cytotoxic response against tumor cells. Our investigation illuminates the intricate metabolic reprogramming occurring within the TME of LUAD in response to neoadjuvant chemotherapy. Specifically, our study highlights the discernible impact on the composition and functionality of immune cells, notably macrophages and T cells. These insights not only deepen our understanding of the nuanced interactions within the TME but also open avenues for the development of novel targeted therapeutic interventions for LUAD.

### Competing Interest Statement

The authors have declared no competing interest.

*   LUAD
    :   lung adenocarcinoma
    NCT
    :   neoadjuvant chemotherapy
    TME
    :   tumor microenvironment
    TSNE
    :   t-distributed random neighborhood embedding
    CNV
    :   copy number variation
    SCENIC
    :   Single-Cell Regulatory Network Inference and Clustering
    SMC
    :   smooth muscle cells
    TCA cycle
    :   pyruvate metabolism and citrate cycle
    TAM
    :   Tumor-Associated Macrophages
    CTLs
    :   cytotoxic T cells
    OXPHOS
    :   oxidative phosphorylation
    CSC
    :   cancer stem cell

Unveiling neoadjuvant chemotherapy-induced immune landscape remodeling and metabolic reprogramming in lung adenocarcinoma by scRNA-sequencing

화학요법이-폐선암-미세환경의-면역-조경-및-대사-재프로그래밍에-미치는-영향-단일세포-rna-시퀀싱을-통한-탐구


화학요법이 폐선암 미세환경의 면역 조경 및 대사 재프로그래밍에 미치는 영향 - 단일세포 RNA 시퀀싱을 통한 탐구
