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Proteins, Expression, Isolation and Analysis | For intracellular cytokine staining (ICS) of ex vivo stimulated lymphocytes, 106 cells per samples were cultured in DMEM containing 2% FBS and Golgiplug (Fisher Scientific, 1.5 ml/ml) for 6 hr with either a peptide pool (5 ug/ml for each peptide) including all CD8+ T cell epitopes expressed by gDMelapoly (mTrp-1455-463: TAPDNLGYA, mTrp-1481-489: IAVVAALLL, mTrp-2522-529: YAEDYEEL, hTp-2180-188: SVYDFFVWL, hTrp-2343-357: STFSFRNAL, mTrp-2363-371: SQVMNLHNL, hgp10025-33: KVPRNQDWL, mBraf 594-602: FGLANEKSI); the E7 peptide: RAHYNIVTTF or SIINFEKL peptide (all from Genscript) or a rabies virus glycoprotein control peptide. | Get A Quote |
How tumor-infiltrating T lymphocytes (TILs) adapt to the metabolic constrains within the tumor microenvironment (TME) and to what degree this affects their ability to combat tumor progression remain poorly understood. Using mouse melanoma models, we report that CD8 TILs enhance peroxisome proliferator-activated receptor (PPAR)-α signaling and catabolism of fatty acids (FAs) when simultaneously subjected to hypoglycemia and hypoxia. This metabolic switch partially preserves CD8 TILs' effector functions, although co-inhibitor expression increases during tumor progression regardless of CD8 TILs' antigen specificity. Further promoting FA catabolism improves the CD8 TILs' ability to slow tumor progression. PD-1... More