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Quantitative phenotyping and spatial analyses, including cellular neighborhoods (CNs), nearest neighbors (NNs\u2009=\u20095-20), and spatial proximity profiling (25-100\u2009\u03bcm), were performed to assess immune architecture and clinical correlations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>EGFR- and KRAS-mutant tumors showed higher tumor cell density and reduced immune infiltration compared with wild-type tumors. Both mutation types were associated with depletion of cytotoxic T cells, dendritic cells, and granulocytes, while EGFR-mutant tumors showed enrichment of M2-like tumor-associated macrophages (TAMs). Cellular neighborhoods analysis identified 14 spatial clusters, with reduced cytotoxic and helper T cell\u2013rich neighborhoods in mutant tumors. Nearest neighbors analysis revealed shorter distances between M2-like TAMs in EGFR-mutant tumors and greater immune exclusion in nonmutants. Spatial proximity revealed higher densities of regulatory T cells and TAMs near tumor cells in KRAS-mutant tumors. All spatial metrics correlated significantly with prognosis in Cox proportional hazards models, highlighting immune cell positioning as an important predictor of outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EGFR- and KRAS-mutant tumors remodel the NSCLC immune landscape, creating distinct immunosuppressive and immune-excluded niches. Spatial proteomics reveals prognostic immune architectures that may guide mutation-directed immunotherapy strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajrccm\/aamag330","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:48:48Z","timestamp":1782301728000},"page":"2778-2791","source":"Crossref","is-referenced-by-count":2,"title":["Spatial proteomics profiling reveals oncogene-specific immune niches and prognostic markers in non-small cell lung cancer"],"prefix":"10.1093","volume":"212","author":[{"given":"Rajender","family":"Nandigama","sequence":"first","affiliation":[{"name":"Institute for Lung Health (ILH), Justus Liebig University , Giessen,","place":["Germany"]},{"name":"Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI) , Bad 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