1356P - Transcriptomic inflammatory profiling of non-small cell lung cancer: Insights from a 7-gene expression analysis

Background

Multiplex RNA techniques can provide an integrated portrait of the tumour immune context. Understanding and characterizing the immune microenvironment in non-small cell lung cancer (NSCLC) remains essential.

Methods

Herein, we examined the immune microenvironment of NSCLC patients (pts) using a customized RNA panel (nCounter, NanoString Technologies) comprising various inflammatory genes (PD-L1, PD-1, CD4, CD8A, FOXP3, GZMM, INFG). Additionally, PD-L1 status was also assessed by immunohistochemistry (IHC; 22C3 clone). Clinical parameters, stage, and outcomes were gathered for analysis, and statistical analyses were conducted using SPSS V26 and RStudio.

Results

The study comprised 545 NSCLC pts, of which PD-L1 IHC was available for 421 (77%). Expression levels of T-cell related genes CD8A, CD4, and GZMM were notably higher in early-stage tumors (n=79, 15%) compared to locally advanced (n=73, 13%; p=. 002,. 027,. 006, respectively) and advanced NSCLC (n=393, 72%; p=. 000 for all genes). Advanced pts with available clinical data (n=166) were clustered into 5 different groups based on the expression of the 7 inflammatory genes: Cluster 1 (n=33, 20%), Cluster 2 (n=24, 14%), Cluster 3 (n=66, 40%), Cluster 4 (n=21, 13%), and Cluster 5 (n=22, 13%). Clusters were balanced according to pts characteristics (histology, sex, smoking status and genomic profile). Among pts treated with immune checkpoint inhibitors (n=72), pts in Cluster 5 were associated with significantly better progression-free survival (PFS; p=. 02). The predictive PFS value of Cluster 5 remained significant, even when grouping pts based on PD-L IHC (PD-L1≥1%, n=56, p=.04; PD-L1≥50%, n=35, p=.003).

Conclusions

Our study unveils differential immune-related RNA expression patterns in NSCLC by stage and underscores the potential utility of immune-signatures as predictive biomarkers of immune response even in patients with high PD-L1 expression levels.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Teixido: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck Sharp & Dohme, Roche Farma, Diaceutics, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: Novartis, AstraZeneca. N. Reguart Aransay: Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, Bayer, Boehringer, Pfizer, Novartis, Sanofi, Janssen, AstraZeneca, Amgen, Novartis, Merck, Janssen, AbbVie; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, BMS, Amgen, Novartis, Sanofi, Merck; Non-Financial Interests, Principal Investigator, PI of Investigator Initiated Trial (PEERS) sponsored by MSD: MSD. All other authors have declared no conflicts of interest.