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A monocyte-centered framework for predicting immunochemotherapy efficacy in lung squamous cell carcinoma patients.

Abstract

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

Authors: Zhao J, Wang Z, Xiao M, Zhang Y, Liu B, Chen S, Tian Y, Lv D, Wang P, Song H, Wu Y, Liu J, Wang K.
Journal: EMBO Mol Med . 2026 Mar 30. doi: 10.1038/s44321-026-00410-y.
Year: 2026
PubMed: PMID: 41912871 (Go to PubMed)