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512 Terminally exhausted CD8+ T cells potentiate the tolerogenic tumor microenvironment as functional suppressors by Vignali, Paolo ;DePeaux, Kristin ;Watson, McLane ;Menk, Ashley ;Scharping, Nicole ;Delgoffe, Greg is a Medicine article available to read on EtoBox.
What is 512 Terminally exhausted CD8+ T cells potentiate the tolerogenic tumor microenvironment as functional suppressors about?
Background Blockade of co-inhibitory ‘checkpoint’ molecules, PD-1 and CTLA-4, has induced impressive clinical responses in advanced tumors; yet only in a subset of patients.1–3 Limited success with checkpoint blockade therapy suggests other cell extrinsic or intrinsic mechanisms may be dampening an effective immune response. Cytotoxic CD8+ T cells (CTL) encountering chronic antigen and metabolic restriction can differentiate to a terminally exhausted state (Texh), marked by hyporesponsiveness and metabolic, epigenetic, and transcriptional dysfunction.4–8 While enrichment of this population in tumor is a negative prognostic factor,9–10 it remains unclear whether Texh are simply non-functional or instead possess tolerogenic or suppressive properties. Transcriptional profiling of tumor-infiltrating PD-1int (progenitor exhausted) CTL versus PD-1hiTIM-3+ (terminally exhausted; Texh), reveals that exhausted cells express a pattern of genes associated with immune suppression. We hypothesize that Texh potentiate the suppressive microenvironment of solid tumor by autoregulation and inhibition of local immune responses. Methods T cell populations were isolated from murine melanoma–B16-F10 or
Who reads 512 Terminally exhausted CD8+ T cells potentiate the tolerogenic tumor microenvironment as functional suppressors?
It is typically read by researchers, students, and practitioners in Medicine.
- Author
- Vignali, Paolo ;DePeaux, Kristin ;Watson, McLane ;Menk, Ashley ;Scharping, Nicole ;Delgoffe, Greg
- Publisher
- BMJ Publishing Group Ltd
- Published
- 2020
- Language
- EN
- Field
- Medicine (Health Sciences)