---
title: Non-small cell lung cancer molecular subtypes and vulnerability to immunotherapy treatment combinations
description: Non-small cell lung cancer molecular subtypes and vulnerability to immunotherapy treatment combinations
---

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# [Non-small cell lung cancer molecular subtypes and vulnerability to immunotherapy treatment combinations](https://www.pathai.com/publications/non-small-cell-lung-cancer-molecular-subtypes-and-vulnerability-to-immunotherapy-treatment-combinations)

 Written by [Admin](https://www.pathai.com/publications/author/admin) | Dec 3, 2025 5:00:00 AM

## Abstract

 

The phase 3 IMpower150 trial in treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC) demonstrates significantly longer progression-free (PFS) and overall survival (OS) with first-line atezolizumab (anti-PD-L1)-bevacizumab (anti-VEGF)-carboplatin-paclitaxel (ABCP) than with bevacizumab-carboplatin-paclitaxel (BCP). We characterise four molecular NSCLC subtypes identified by unsupervised clustering of transcriptomes of 564 pre-treatment primary tumour samples from IMpower150 using non-negative matrix factorization (NMF1-4). Each subtype has distinct tumour PD-L1 expression levels, epithelial characteristics, immune composition, and treatment outcomes. Both NMF2 (enriched in tumour proliferation signal, macrophages, and monocytes) and NMF4 (enriched in B cells and T cells) have elevated tumour PD-L1 expression. Of these two, only NMF4 demonstrates PFS and OS benefits with ABCP versus either BCP or atezolizumab-carboplatin-paclitaxel (ACP). Patients with NMF1 (enriched in basal and squamous-like cells) have improved outcomes on ABCP compared with ACP or BCP; those with NMF3 (enriched in adenocarcinoma signatures) show similar outcomes among treatments. These insights could help inform individualised first-line treatment for metastatic NSCLC.

[View Publication](https://www.nature.com/articles/s41467-025-66803-8)

[View full post](https://www.pathai.com/publications/non-small-cell-lung-cancer-molecular-subtypes-and-vulnerability-to-immunotherapy-treatment-combinations)

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