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Despite the presence of immune cells, tumor cells orchestrate a tumor\u2010supportive environment through intricate interaction with the components of the TME. However, the specific mechanism by which this intercellular dialogue is regulated is not fully understood. To that end, the development of an organotypic 3D breast TME\u2010on\u2010a\u2010chip (TMEC) model, integrated with single\u2010cell RNA sequencing analysis, is reported to mechanistically evaluate the progression of triple\u2010negative breast cancer (TNBC) cells in the presence of patient\u2010derived CAFs and M\u03c6s. Extensive functional assays, including invasion and morphometric characterization, reveal the synergistic influence of CAFs and M\u03c6s on tumor cells. Furthermore, gene expression and pathway enrichment analyses identify the involvement of the\n                    <jats:italic>KYNU<\/jats:italic>\n                    gene, suggesting a potential immune evasion mechanism through the kynurenine pathway. 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