Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells

LUAD 的综合单细胞分析:基于耗竭的 CD8+ T 细胞阐明免疫细胞动力学和预后模型

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作者:Han Zhang #, Pengpeng Zhang #, Xuefeng Lin #, Lin Tan #, Yuhang Wang, Xiaoteng Jia, Kai Wang, Xin Li, Daqiang Sun

Background

The tumor microenvironment (TME) plays a pivotal role in the progression and metastasis of lung adenocarcinoma (LUAD). However, the detailed characteristics of LUAD and its associated microenvironment are yet to be extensively explored. This study aims to delineate a comprehensive profile of the immune cells within the LUAD microenvironment, including CD8+ T cells, CD4+ T cells, and myeloid cells. Subsequently, based on marker genes of exhausted CD8+ T cells, we

Conclusion

The creation of a LUAD single-cell atlas in our study offered new insights into its tumor microenvironment and immune cell interactions, highlighting the importance of key genes associated with exhausted CD8+ T cells. These discoveries have enabled the development of an effective prognostic model for LUAD and identified GALNT2 as a potential therapeutic target, significantly contributing to the improvement of LUAD diagnosis and treatment strategies.

Results

Our study developed a single-cell atlas for LUAD from scRNA-seq data of 19 patients, examining crucial immune cells in LUAD's microenvironment. We underscored pDCs' role in antigen processing and established a Cox regression model based on CD8_Tex-LAYN genes for risk assessment. Additionally, we contrasted prognosis and tumor environments across risk groups, constructed a new nomogram integrating clinical features, validated the expression of model genes via RT-PCR, and confirmed GALNT2's function in LUAD through cellular experiments, thereby enhancing our understanding and approach to LUAD treatment.

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