血浆细胞外囊泡转录组学鉴定 CD160 用于预测肺癌免疫化疗疗效

Better biomarkers are needed to improve the efficacy of immune checkpoint inhibitors in lung adenocarcinoma (LUAD) treatment.

We investigated the plasma extracellular vesicle (EV)-derived long RNAs (exLRs) in unresectable/advanced LUAD to explore biomarkers for immunochemotherapy. Seventy-four LUAD patients without targetable mutations receiving first-line anti-programmed cell death 1 (PD-1) immunochemotherapy were enrolled. Their exLRs were profiled through plasma EV transcriptome sequencing. Biomarkers were analyzed against response rate and survival using pre- and post-treatment samples in the retrospective cohort (n = 36) and prospective cohort (n = 38). The results showed that LUAD patients demonstrated a distinct exLR profile from the healthy individuals (n = 56), and T-cell activation-related pathways were enriched in responders.

Among T-cell activation exLRs, CD160 exhibited a strong correlation with survival. In the retrospective cohort, the high baseline EV-derived CD160 level correlated with prolonged progression-free survival (PFS) (P < 0. 001) and overall survival (OS) (P = 0. 005), with an area under the curve (AUC) of 0.

784 for differentiating responders from non-responders. In the prospective cohort, the CD160-high patients also showed prolonged PFS (P = 0. 003) and OS (P = 0. 014) and a promising AUC of 0. 648. The predictive value of CD160 expression was validated by real-time quantitative PCR.

We also identified the dynamics of EV-derived CD160 for monitoring therapeutic response. The elevated baseline CD160 reflected a higher abundance of circulating NK cells and CD8 + -naïve T cells, suggesting more active host immunity.

In addition, increased CD160 levels of tumors also correlated with a favorable prognosis in LUAD patients.

Together, plasma EV transcriptome analysis revealed the role of the baseline CD160 level and early post-treatment CD160 dynamics for predicting the response to anti-PD-1 immunochemotherapy in LUAD patients.