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Suppression of the TIME is driven by multiple mechanisms including increased expression of immune checkpoint molecules like programmed death-ligand 1 (PD-L1) on tumors and their cognate programmed cell death protein-1 (PD-1) receptors on lymphocytes, or decreased generation/presentation of mutation-based or expression-based neoantigens by cancer cells.8 9 However, there is now increasing evidence that altered metabolic activity inside tumor cells plays a critical role in the recruitment of suppressive cells and the exhaustion of effector cells including CD8 +tumor infiltrating lymphocytes (TILs).1013 A reduction of oxidative phosphorylation and increased production of lactate has broad based suppressive effects on functional immunocytes and has been shown by us and others to generate cold tumors depleted of effector cells.12 14 Modulation of the kynurenine pathway through differential activation of indoleamine 2,3 dioxygenase has also been shown to cause T-cell anergy, increase proliferation of T-regs and alter the overall balance of the Th1/Th2 response.15 Just how broadly relevant these phenomena are remains unclear

D., & Muc, A

First, the cells were resuspended by cell staining buffer (BioLegend, 420201) and blocked with Human TruStain FcX Fc Blocking reagent (BioLegend) at 4C for 10 minutes

GS: Writing review & editing, Writing original draft, Resources