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- W4313366001 abstract "Abstract T cell-based therapies have shown promising results, but adoptive T cell therapy (ACT) for solid tumors like melanoma treatment has met limited success. The goal of this study was to identify attributes of T cell fitness important for optimal anti-tumor efficacy. This was accomplished by integrated profiling of expanded tumor infiltrating lymphocytes, TILs (responders (CR) and progressive diseases (PD)) co-cultured overnight with their autologous primary tumor cells with the aid of a suite of single-cell, transcriptional, proteomic and functional assays to construct a genome-scale metabolic model of the metabolism of TILs and tumor cells in direct competition with each other. Sorted live TILs after co-culture were used to performed RNA-seq, and proteome-wide profiling by mass spectrometry. Gene enrichment of the CR TIL suggested an increased expression in genes involving processes such as glycolysis, hypoxia, adipogenesis, and mTORC1 signaling. PD tumors showed an increase for epithelial to mesenchymal transition (EMT) and glycolysis. Comparisons of transcripts and proteins in both CR and PD were tightly correlated (Spearman rank 0.765). Since patient-derived cell numbers were limited (<50,000), we utilized genome-scale metabolic models to infer relevant metabolic pathways by comparison to the human metabolic Atlas (HMR2). We observed high enrichment in fatty acid β-oxidation processes in different organelles related to CR TIL and tumor. Lastly, we examined if increasing fatty acid oxidation in TILs might enable their increased survival in metabolically replete environments. These results show that the fatty acid metabolism pathway is associated with the ACT efficacy, and it can contribute to improving treatment." @default.
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- W4313366001 date "2019-05-01" @default.
- W4313366001 modified "2023-09-26" @default.
- W4313366001 title "Integrated profiling of T cells and tumor cells demonstrates metabolic adaptation essential for melanoma cell therapy" @default.
- W4313366001 doi "https://doi.org/10.4049/jimmunol.202.supp.134.6" @default.
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