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

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.