A spatial immune scoring system based on the tumor microenvironment features improves prognostic stratification in lung adenocarcinoma.

The spatial heterogeneity of the tumor immune microenvironment (TME) in lung adenocarcinoma (LUAD) limits the prognostic accuracy of traditional TNM staging. Moreover, conventional T cell based immune scores established for other solid tumors fail to effectively stratify patient outcomes in LUAD. To address this, we applied quantitative multiplex immunofluorescence to map the spatial immune contexture of LUAD and developed the Lung Cancer Immune Score (LCIS). This framework integrates four key biomarkers: CD68⁺HLA-DR⁺ macrophages, CD20⁺ B cells, PD-1⁺ cells and Ki67⁺ proliferating tumor cells, to quantify the balance between tumor proliferation and host anti-tumor immunity across the tumor core and invasive margin. High LCIS scores independently predicted improved overall survival in both the discovery (p = 0.02) and independent validation (p = 0.017) cohorts, outperforming conventional clinical parameters and single biomarkers. Specifically, LCIS effectively sub-stratified patients with Stage II and III LUAD into refined prognostic groups, resolving the prognostic ambiguity within the same TNM stage. Overall, by quantifying the interaction between tumor proliferation and antigen-directed immune activation, the LCIS serves as a spatial biomarker to refine prognosis and inform personalized therapy in LUAD.