地图集(解剖学)
组织重塑
肺
腺癌
病理
医学
内科学
解剖
癌症
炎症
作者
William Zhao,Benjamin Kepecs,Navin R. Mahadevan,Åsa Segerstolpe,Jason L. Weirather,N. Besson,Bruno Giotti,Brian Y. Soong,Chendi Li,Sébastien Vigneau,Michal Slyper,Isaac Wakiro,Judit Jané‐Valbuena,Orr Ashenberg,Asaf Rotem,Raphael Bueno,Orit Rozenblatt-Rosen,Kathleen L. Pfaff,Scott J. Rodig,Aaron N. Hata,Aviv Regev,Bruce E. Johnson,Alexander Tsankov
标识
DOI:10.1101/2023.06.28.546977
摘要
Abstract TP53 is the most frequently mutated gene across many cancers and is associated with shorter survival in non-small cell lung cancer (NSCLC). To understand how TP53 -mutant ( TP53 mut ) malignant cells interact with the tumor microenvironment (TME) at a molecular, cellular, and tissue level, we built a multi-omic cellular and spatial tumor atlas of 23 treatment-naïve NSCLC human tumors. We identified significant differences in malignant expression programs and spatial cell-cell interactions between TP53 mut and TP53 WT tumors and found that highly-entropic TP53 mut malignant cells lose alveolar identity and coincide with an increased abundance of exhausted T cells and immune checkpoint interactions with implications for response to checkpoint blockade. We also identified a multicellular, pro-metastatic, hypoxic tumor niche, where highly-plastic, TP53 mut malignant cells expressing epithelial to mesenchymal transition (EMT) programs associate with SPP1 + myeloid cells and collagen-expressing cancer-associated fibroblasts. Our approach can be further applied to investigate mutation-specific TME changes in other solid tumors.
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