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However, the characteristics of different organ\u2010tropism metastases of GC are largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ten fresh human tissue samples from six patients, including primary tumour and adjacent non\u2010tumoural samples and six metastases from different organs or tissues (liver, peritoneum, ovary, lymph node) were evaluated using single\u2010cell RNA sequencing. Validation experiments were performed using histological assays and bulk transcriptomic datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Malignant epithelial subclusters associated with invasion features, intraperitoneal metastasis propensity, epithelial\u2013mesenchymal transition\u2010induced tumour stem cell phenotypes, or dormancy\u2010like characteristics were discovered. High expression of the first three subcluster\u2010associated genes displayed worse overall survival than those with low expression in a GC cohort containing 407 samples. Immune and stromal cells exhibited cellular heterogeneity and created a pro\u2010tumoural and immunosuppressive microenvironment. Furthermore, a 20\u2010gene signature of lymph node\u2010derived exhausted CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells was acquired to forecast lymph node metastasis and validated in GC cohorts. Additionally, although anti\u2010NKG2A (KLRC1) antibody have not been used to treat GC patients even in clinical trials, we uncovered not only malignant tumour cells but one endothelial subcluster, mucosal\u2010associated invariant T cells, T cell\u2010like B cells, plasmacytoid dendritic cells, macrophages, monocytes, and neutrophils may contribute to HLA\u2010E\u2010KLRC1\/KLRC2 interaction with cytotoxic\/exhausted CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and\/or natural killer (NK) cells, suggesting novel clinical therapeutic opportunities in GC. Additionally, our findings suggested that PD\u20101 expression in CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells might predict clinical responses to PD\u20101 blockade therapy in GC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provided insights into heterogeneous microenvironment of GC primary tumours and organ\u2010specific metastases and provide support for precise diagnosis and treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.730","type":"journal-article","created":{"date-parts":[[2022,2,20]],"date-time":"2022-02-20T14:27:23Z","timestamp":1645367243000},"source":"Crossref","is-referenced-by-count":262,"title":["Revealing the transcriptional heterogeneity of organ\u2010specific metastasis in human gastric cancer using single\u2010cell RNA 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