Tumors are heterogeneous cellular environments with entwined metabolic dependencies. Here, we used a tumor transcriptome deconvolution approach to profile the metabolic states of cancer and non-cancer (stromal) cells in bulk tumors of 20 solid tumor types. We identified metabolic genes and processes recurrently altered in cancer cells across tumor types, including pan-cancer upregulation of deoxythymidine triphosphate (dTTP) production. In contrast, the tryptophan catabolism rate limiting enzymes, IDO1 and TDO2, were highly overexpressed in stroma, suggesting that kynurenine-mediated suppression of antitumor immunity is predominantly constrained by the stroma. Oxidative phosphorylation was unexpectedly the most upregulated metabolic process in cancer cells compared to both stromal cells and a large atlas of cancer cell lines, suggesting that the Warburg effect may be less pronounced in cancer cells in vivo. Overall, our analysis highlights fundamental differences in metabolic states of cancer and stromal cells inside tumors and establishes a pan-cancer resource to interrogate tumor metabolism.

中文翻译：

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肿瘤微环境的全癌代谢图谱

肿瘤是具有交织的代谢依赖性的异质细胞环境。在这里，我们使用了肿瘤转录组反卷积方法来分析20种实体瘤类型的大块肿瘤中癌症和非癌（基质）细胞的代谢状态。我们确定了跨肿瘤类型在癌细胞中反复改变的代谢基因和过程，包括三磷酸脱氧胸苷（dTTP）生产的全癌基因上调。相比之下，色氨酸分解代谢速率限制酶IDO1和TDO2，在基质中高度过表达，表明犬尿氨酸介导的抗肿瘤免疫抑制主要受基质限制。与基质细胞和大型癌细胞系图谱相比，氧化磷酸化出乎意料地是癌细胞中最上调的代谢过程，这表明沃堡效应在体内癌细胞中可能不那么明显。总体而言，我们的分析突出了肿瘤和肿瘤内部基质细胞代谢状态的根本差异，并建立了一种泛癌资源来询问肿瘤代谢。