Divergent Tumor Immune Microenvironment and Response to Neoadjuvant Chemoimmunotherapy in Resectable Non-Small Cell Lung Cancer: A Single-Arm Phase II Trial.

Authors

Minjiang Chen, Rongzhen Li, Zuolin Cheng, Yuxi Wei, Hongsheng Liu, Xiaoyun Zhou, Jing Zhao, Li Zhang, Wei Zhong, Bo Huang, Guoqiang Yu, Ji Li, Yan Xu, Mengzhao Wang

Published in

Clinical cancer research : an official journal of the American Association for Cancer Research. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

Neoadjuvant chemoimmunotherapy improves outcomes in resectable non-small cell lung cancer (NSCLC), yet the spatial immune features associated with treatment response remain unclear.
In this single-arm phase II trial (NCT05383716), patients with resectable NSCLC received neoadjuvant pembrolizumab plus platinum-based chemotherapy, followed by surgery and adjuvant immunotherapy. The primary endpoint was major pathological response (MPR). Digital spatial profiling was performed on resected tumors and paired draining lymph nodes from 22 patients, with additional tumor samples collected for validation.
Among 80 enrolled patients, 55 underwent surgery, achieving an MPR rate of 37.5% and a pathological complete response rate of 26.3%. Grade 3-4 treatment-related adverse events occurred in 26.3% of patients. Spatial transcriptomics showed that MPR tumors were enriched for T- and B-cell activation pathways and infiltration of CD8+ T cells, B cells, plasma cells, and T-follicular helper cells, whereas non-MPR tumors exhibited stress adaptation and immune suppression signatures. Two immune phenotypes were identified within MPR samples: myeloid-enriched (ME) and lymphoid-enriched (LE) subtypes. The LE subtype was associated with improved response and survival in validation cohorts, whereas higher ME scores showed a trend toward poorer survival. An 18-gene LE signature was developed as a potential biomarker for adjuvant immunotherapy benefit.
Neoadjuvant pembrolizumab plus chemotherapy demonstrated encouraging efficacy and manageable safety in resectable NSCLC. Spatial profiling identified distinct immune phenotypes associated with response and may inform patient stratification for adjuvant therapy.

PMID:
42440361
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.