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DataCite Commons2024-07-29 更新2024-08-19 收录
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https://figshare.com/articles/dataset/Source_Data/26384302
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Tumor draining lymph nodes (TDLN) represent a key component of the tumor-immunity cycle. There are few studies describing how TDLNs impact lymphocyte infiltration into tumors. Here we directly compare tumor-free TDLNs draining “cold” and “hot” human triple negative breast cancers (TDLN<sub>Cold</sub> and TDLN<sub>Hot</sub>). Using machine-learning-based self-correlation analysis of immune gene expression, we find unbalanced intranodal regulations within TDLN<sub>Cold</sub>. Two gene pairs (<i>TBX21</i>/<i>GATA3</i>-<i>CXCR1</i>) with opposite correlations suggest preferential priming of T helper 2 (Th2) cells by mature dendritic cells (DC) within TDLN<sub>Cold</sub>. This is validated by multiplex immunofluorescent staining, identifying more mature-DC-Th2 spatial clusters within TDLN<sub>Cold </sub>versus TDLN<sub>Hot</sub>. Associated with this Th2 priming preference, more IL4 producing mast cells (MC) are found within sinus regions of TDLN<sub>Cold</sub>. Downstream, Th2-associated fibrotic TME is found in paired cold tumors with increased Th2/T-helper-1-cell (Th1) ratio, upregulated fibrosis growth factors, and stromal enrichment of cancer associated fibroblasts. These findings are further confirmed in a validation cohort and public genomic data. Our results reveal a potential role of IL4<sup>+</sup> MCs within TDLNs, associated with Th2 polarization and reduced immune infiltration into tumors.
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figshare
创建时间:
2024-07-26
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