Lung Cancer is a malignant disease characterized by uncontrolled cell growth in the tissues of the lung. It is one of the leading causes of cancer-related deaths worldwide. Diagnosis and treatment depend on early detection through imaging and molecular biomarkers. Advances in genomics and machine learning have improved predictive diagnostics and personalized therapy selection. Research continues to focus on prevention, early screening, and novel therapeutic targets.

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Spatial Signatures for Predicting Immunotherapy Outcomes Using Multi-Omics in Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) shows variable responses to immunotherapy, highlighting the need for biomarkers to guide patient selection. We applied a spatial multi-omics approach to 234 advanced NSCLC patients treated with programmed death 1-based immunotherapy across three cohorts to identify biomarkers associated with outcome. Spatial proteomics (n?=?67) and spatial compartment-based transcriptomics (n?=?131) enabled profiling of the tumor immune microenvironment (TIME). Using spatial proteomics, we identified a resistance cell-type signature including proliferating tumor cells, granulocytes, vessels (hazard ratio (HR)?=?3.8, P?=?0.004), and a response signature, including M1/M2 macrophages and CD4 T cells (HR?=?0.4, P?=?0.019). We then generated a cell-to-gene resistance signature using spatial transcriptomics, which was predictive of poor outcomes (HR?=?5.3, 2.2, 1.7 across Yale, University of Queensland and University of Athens cohorts), while a cell-to-gene response signature predicted favorable outcomes (HR?=?0.22, 0.38 and 0.56, respectively). This framework enables robust TIME modeling and identifies biomarkers to support precision immunotherapy in NSCLC.