{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:34:09Z","timestamp":1792139649818,"version":"4.4.0"},"reference-count":75,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Conventional immunohistochemistry technologies were limited by the inability to simultaneously detect multiple markers and the lack of identifying spatial relationships among cells, hindering understanding of the biological processes in cancer immunology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tissue slices of primary tumours from 553 IA\u223cIIIB non\u2010small cell lung cancer (NSCLC) cases were stained by multiplex immunofluorescence (mIF) assay for 10 markers, including CD4, CD38, CD20, FOXP3, CD66b, CD8, CD68, PD\u2010L1, CD133 and CD163, evaluating the amounts of 26 phenotypes of cells in tumour nest and tumour stroma. StarDist depth learning model was utilised to determine the spatial location of cells based on mIF graphs. Single\u2010cell RNA sequencing (scRNA\u2010seq) on four primary NSCLC cases was conducted to investigate the putative cell interaction networks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Spatial proximity among CD20+ B cells, CD4+ T cells and CD38+ T cells (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.41) was observed, whereas the distribution of regulatory T cells was associated with decreased infiltration levels of CD20+ B cells and CD38+ T cells (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a0\u22120.45). Univariate Cox analyses identified closer proximity between CD8+ T cells predicted longer disease\u2010free survival (DFS). In contrast, closer proximity between CD133+ cancer stem cells (CSCs), longer distances between CD4+ T cells and CD20+ B cells, CD4+ T cells and neutrophils, and CD20+ B cells and neutrophils were correlated with dismal DFS. Data from scRNA\u2010seq further showed that spatially adjacent N1\u2010like neutrophils could boost the proliferation and activation of T and B lymphocytes, whereas spatially neighbouring M2\u2010like macrophages showed negative effects. An immune\u2010related risk score (IRRS) system aggregating robust quantitative and spatial prognosticators showed that high\u2010IRRS patients had significantly worse DFS than low\u2010IRRS ones (HR 2.72, 95% CI 1.87\u20133.94, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We developed a framework to analyse the cell interaction networks in tumour microenvironment, revealing the spatial architecture and intricate interplays between immune and tumour cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1155","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T03:27:30Z","timestamp":1672630050000},"source":"Crossref","is-referenced-by-count":81,"title":["Multiplex immunofluorescence and single\u2010cell transcriptomic profiling reveal the spatial cell interaction networks in the non\u2010small cell lung cancer 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