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The single\u2010cell transcriptomic atlas of PT (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04) and paired tumour\u2010draining lymph nodes (TDLNs) (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05 for tumour\u2010invaded,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a03 for tumour\u2010free) microenvironment was profiled. Various bioinformatics analyses based on Gene Expression Omnibus, TCGA and Array\u2010Express databases were also used to validate the discoveries.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Spatial distances of CD4+ T cells\u2013CD38+ T cells, CD4+ T cells\u2013neutrophils and CD38+ T cells\u2013neutrophils prolonged and they were replaced by CD163+ macrophages in PT along with tumour progression. Neutrophils showed unique stage and location\u2010dependent prognostic effects. A high abundance of stromal neutrophils improved disease\u2010free survival in the early\u2010stage, whereas high intratumoural neutrophil infiltrates predicted poor prognosis in the mid\u2010to\u2010late\u2010stage. Significant molecular and functional reprogramming in PT and TDLN microenvironments was observed. Diverse interaction networks mediated by neutrophils were found between positive and negative TDLNs. Five phenotypically and functionally heterogeneous subtypes of tumour\u2010associated neutrophil (TAN) were further identified by pseudotime analysis, including TAN\u20100 with antigen\u2010presenting function, TAN\u20101 with strong expression of interferon (IFN)\u2010stimulated genes, the pro\u2010tumour TAN\u20102 subcluster, the classical subset (TAN\u20103) and the pro\u2010inflammatory subtype (TAN\u20104). Loss of IFN\u2010stimulated signature and growing angiogenesis activity were discovered along the transitional trajectory. Eventually, a robust six neutrophil differentiation relevant genes\u2010based model was established, showing that low\u2010risk patients had longer overall survival time and may respond better to immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The cellular composition, spatial location, molecular and functional changes in PT and TDLN microenvironments along with NSCLC progression were deciphered, highlighting the immunoregulatory roles and evolutionary heterogeneity of TANs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.1340","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:20:36Z","timestamp":1690330836000},"source":"Crossref","is-referenced-by-count":35,"title":["Cellular dynamics in tumour microenvironment along with lung cancer progression underscore spatial and evolutionary heterogeneity of 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