Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Integrated Traditional Chinese and Western Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
J Gene Med. 2024 Sep;26(9):e3736. doi: 10.1002/jgm.3736.
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.
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.
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.
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.
免疫疗法代表了癌症治疗领域的一项突破性和里程碑式的成就，标志着在对抗这种毁灭性疾病方面取得了重大进展。肺癌对免疫治疗的反应持续显示出临床改善，但不可否认的是，应答率有限、获得性耐药以及基础机制不明确等问题仍然存在。
通过对 GSE207422 中 MPR（主要病理反应）和 NMPR（非主要病理反应）样本的单细胞 RNA 测序（scRNA-seq）分析，定义和区分了细胞组成，包括四个原发性 MPR 样本和八个原发性 NMPR 样本。
我们发现 MPR 和 NMPR 样本之间 CD8+T 细胞群体存在明显差异，NMPR 样本中 TYMS、RRM2 和 BIRC5 表达较高。同时，NMPR 样本中巨噬细胞和肿瘤上皮细胞浸润的比例增加。我们在上皮细胞中发现了一些潜在的生物标志物（ACTN4、ATF3、BRD2、CDKN1A 和 CHMP4B），这些标志物可能代表了更差的预后。
通过探索不同程度新辅助免疫治疗样本中肿瘤微环境（TME）的差异，本研究为预测治疗反应提供了一些新的生物标志物，并为克服免疫治疗耐药性提供了理论依据。
