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Updated: Aug 5, 2026
Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment
Published on: March 25, 2020
Single-cell and spatial omics in non-small cell lung cancer: dissecting metabolic reprogramming and tumor-immune
Zhenzhen Lian1, Xu Jing Wu1, Yangyang Zhou1
1Department of Pharmacy, Yueqing Hospital of Wenzhou Medical University, Yueqing People's Hospital, Wenzhou, Zhejiang, China.
Abstract:
Non-small cell lung cancer (NSCLC) is often presented as a success story for precision oncology, but that success remains uneven. Targeted agents and immune checkpoint inhibitors have changed treatment for molecularly defined or immune-responsive tumors, yet many patients relapse as resistant clones emerge, tumor cells shift state, and local immune pressure changes across the lesion. Bulk genomic and transcriptomic assays have been useful for clinical stratification, but they average signals across mixed cell populations and therefore miss rare resistant cells, transient drug-tolerant states, and spatially restricted tumor-immune interactions. Single-cell and spatial omics now provide a more direct way to examine these problems. In NSCLC, single-cell RNA sequencing, single-cell chromatin profiling, spatial transcriptomics, and multiplex imaging have begun to map malignant epithelial plasticity, persister-like states, dysfunctional immune compartments, stromal remodeling, and metabolically distinct niches. These approaches do not simply add resolution; they help connect cell state, metabolic activity, tissue location, and treatment response. This mini review discusses how single-cell and spatial omics are reshaping our understanding of metabolic reprogramming and tumor-immune ecosystems in NSCLC, and how these findings may inform biomarker discovery, patient stratification, resistance monitoring, and rational combination therapy.
Insights
Single-cell and spatial omics reveal complex changes in non-small cell lung cancer (NSCLC) that lead to treatment resistance. These advanced techniques offer new insights into tumor cell plasticity and the tumor-immune microenvironment for improved therapies.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Precision oncology has advanced non-small cell lung cancer (NSCLC) treatment, but patient relapse due to resistance remains a challenge.
- Current bulk assays average signals, missing critical details about rare resistant cells, transient states, and spatial tumor-immune interactions.
- Understanding these complex biological dynamics is crucial for overcoming treatment resistance in NSCLC.
Purpose of the Study:
- To review how single-cell and spatial omics are transforming the understanding of metabolic reprogramming and tumor-immune ecosystems in NSCLC.
- To highlight the potential of these omics approaches for biomarker discovery, patient stratification, resistance monitoring, and combination therapy development.
Main Methods:
- Single-cell RNA sequencing
- Single-cell chromatin profiling
- Spatial transcriptomics
- Multiplex imaging
Main Results:
- Single-cell and spatial omics enable detailed mapping of malignant epithelial plasticity and persister-like states.
- These methods reveal insights into dysfunctional immune compartments, stromal remodeling, and metabolically distinct niches within NSCLC tumors.
- These approaches connect cellular states, metabolic activity, tissue location, and treatment response.
Conclusions:
- Single-cell and spatial omics provide unprecedented resolution to study NSCLC heterogeneity and treatment resistance.
- These advanced techniques are essential for discovering new biomarkers, refining patient stratification, monitoring resistance, and designing rational combination therapies for NSCLC.
