Single-cell RNA sequencing reveals microenvironmental infiltration in non-small cell lung cancer with different responses to immunotherapy

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2024-09-03 DOI:10.1002/jgm.3736

Xinnan Hu, Yonghui Wu, Lixin Wang, Fujun Yang, Lingyun Ye, Xiaoxia Chen, Xiao Song, Ping Wei

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引用次数: 0

Abstract

Background

Immunotherapy represents a groundbreaking and monumental achievement in the field of cancer therapy, marking a significant advancement in fighting against this devastating disease. Lung cancer has showed consistent clinical improvements in response to immunotherapy treatments, yet, it is undeniable that challenges such as limited response rates acquire resistance, and the unclear fundamental mechanisms were inevitable problems.

Methods

The cellular composition was defined and distinguished through single-cell RNA sequencing (scRNA-seq) analysis of MPR (major pathologic response) and NMPR (non-major pathologic response) samples in GSE207422, including four primary MPR samples and eight primary NMPR samples.

Results

We found obvious difference in CD8+ T cell population between MPR and NMPR samples, with high expression of TYMS, RRM2, and BIRC5 in NPMR samples. Meanwhile, the proportion of macrophages and tumor epithelial cells infiltration increased in the NMPR samples. We discovered biomarkers (ACTN4, ATF3, BRD2, CDKN1A, and CHMP4B) in epithelial cells which were potentially represented worse outcomes.

Conclusions

By exploring the difference of tumor microenvironment (TME) in samples with different corresponding degrees of neoadjuvant immunotherapy, this research introduces a number of novel biomarkers for predicting the response of treatment and a theoretical basis for overcoming immunotherapy resistance.

Abstract Image

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单细胞 RNA 测序揭示了非小细胞肺癌微环境浸润对免疫疗法的不同反应。

背景：免疫疗法是癌症治疗领域的一项开创性的巨大成就，标志着抗击这一毁灭性疾病的重大进展。肺癌对免疫疗法的临床反应持续改善，但不可否认的是，有限的反应率和耐药性以及基本机制不明等挑战是不可避免的问题：方法：通过单细胞RNA测序（scRNA-seq）分析GSE207422中的MPR（主要病理反应）和NMPR（非主要病理反应）样本，包括4个原发MPR样本和8个原发NMPR样本，确定并区分细胞组成：结果：我们发现MPR和NMPR样本的CD8+T细胞群存在明显差异，NMPR样本中TYMS、RRM2和BIRC5表达量较高。同时，NMPR样本中巨噬细胞和肿瘤上皮细胞浸润比例增加。我们在上皮细胞中发现了生物标记物（ACTN4、ATF3、BRD2、CDKN1A和CHMP4B），这些标记物可能代表着更差的预后：本研究通过探讨新辅助免疫治疗相应程度不同的样本中肿瘤微环境（TME）的差异，提出了一些预测治疗反应的新型生物标志物，为克服免疫治疗耐药性提供了理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.