Immunometabolic coevolution defines unique microenvironmental niches in ccRCC.
Cell Metab
; 35(8): 1424-1440.e5, 2023 08 08.
Article
in En
| MEDLINE
| ID: mdl-37413991
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma
/
Carcinoma, Renal Cell
/
Kidney Neoplasms
Limits:
Humans
Language:
En
Journal:
Cell Metab
Journal subject:
METABOLISMO
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos