[Preliminary Analysis of Tumor Immune Microenvironment Characteristics
in Lung Squamous Cell Carcinoma after...

Neoadjuvant immunochemotherapy has emerged as an important treatment strategy for non-small cell lung cancer (NSCLC); however, substantial heterogeneity in therapeutic response persists among patients. Currently, treatment efficacy is primarily evaluated by imaging modalities, and there remains a lack of comprehensive studies investigating post-treatment alterations in the tumor microenvironment (TME) and their association with clinical response. This study applied single-cell RNA sequencing (scRNA-seq) to characterize TME remodeling in lung squamous cell carcinoma after neoadjuvant immunochemotherapy and to explore its potential association with differences in therapeutic response.

Tumor specimens from two patients with lung squamous cell carcinoma who underwent surgical resection following neoadjuvant immunochemotherapy were subjected to scRNA-seq. An integrated analysis was performed to characterize the cellular composition, functional states, and intercellular communication patterns within the TME.

Preoperative imaging evaluation indicated partial response (PR) in patient 1 and stable disease (SD) in patient 2, whereas postoperative pathological evaluation showed major pathological response (MPR) and partial pathological response (PPR), respectively. ScRNA-seq identified nine major cell populations. The TME exhibited marked heterogeneity between the two patients: patient 1 was characterized by immune cell enrichment and inflammatory activation, whereas patient 2 showed remodeling dominated by myeloid and endothelial signals, together with more prominent immune regulatory and angiogenic features. Cell-cell communication analysis revealed that patient 1 was mainly characterized by inflammatory chemotactic interactions, whereas patient 2 showed enhanced C-X-C motif chemokine ligand (CXCL), secreted phosphoprotein 1 (SPP1), vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF) and tumor necrosis factor (TNF) signaling, along with prominent immunosuppressive interaction axes. In addition, patient 2 showed a relative enrichment of macrophages and a more pronounced exhausted T-cell phenotype.

After neoadjuvant immunochemotherapy, the TME in patients with lung squamous cell carcinoma exhibits marked heterogeneity in terms of cellular composition, functional states, and intercellular communication. The TME remodeling patterns revealed by scRNA-seq may provide insights into discrepancies in treatment response evaluation and help identify potential biomarkers.