Immunometabolic coevolution defines unique microenvironmental niches in ccRCC Journal Article
| Authors: | Tang, C.; Xie, A. X.; Liu, E. M.; Kuo, F.; Kim, M.; DiNatale, R. G.; Golkaram, M.; Chen, Y. B.; Gupta, S.; Motzer, R. J.; Russo, P.; Coleman, J.; Carlo, M. I.; Voss, M. H.; Kotecha, R. R.; Lee, C. H.; Tansey, W.; Schultz, N.; Hakimi, A. A.; Reznik, E. |
| Article Title: | Immunometabolic coevolution defines unique microenvironmental niches in ccRCC |
| Abstract: | Tumor cell phenotypes and anti-tumor immune responses are shaped by local metabolite availability, but intratumoral metabolite heterogeneity (IMH) and its phenotypic consequences remain poorly understood. To study IMH, we profiled tumor/normal regions from clear cell renal cell carcinoma (ccRCC) patients. A common pattern of IMH transcended all patients, characterized by correlated fluctuations in the abundance of metabolites and processes associated with ferroptosis. Analysis of intratumoral metabolite-RNA covariation revealed that the immune composition of the microenvironment, especially the abundance of myeloid cells, drove intratumoral metabolite variation. Motivated by the strength of RNA-metabolite covariation and the clinical significance of RNA biomarkers in ccRCC, we inferred metabolomic profiles from the RNA sequencing data of ccRCC patients enrolled in 7 clinical trials, and we ultimately identifyied metabolite biomarkers associated with response to anti-angiogenic agents. Local metabolic phenotypes, therefore, emerge in tandem with the immune microenvironment, influence ongoing tumor evolution, and are associated with therapeutic sensitivity. © 2023 The Author(s) |
| Keywords: | transcriptomics; tumor marker; renal cell carcinoma; kidney neoplasms; rna; kidney tumor; carcinoma, renal cell; carcinoma; bone marrow cell; myeloid cells; tumor microenvironment; metabolomics; metabolites; imputation; intratumoral heterogeneity; cancer metabolism; humans; human; immune microenvironment; biomarkers, tumor; immunometabolism |
| Journal Title: | Cell Metabolism |
| Volume: | 35 |
| Issue: | 8 |
| ISSN: | 1550-4131 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2023-08-08 |
| Start Page: | 1424 |
| End Page: | 1440.e5 |
| Language: | English |
| DOI: | 10.1016/j.cmet.2023.06.005 |
| PUBMED: | 37413991 |
| PROVIDER: | scopus |
| PMCID: | PMC10603615 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding authors are MSK authors: A. Ari Hakimi and Ed Reznik -- Source: Scopus |
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