CD28
Overview
CD28 is a co-stimulatory receptor expressed on T cells that, upon engagement with CD80 (B7-1) or CD86 (B7-2) on antigen-presenting cells, provides the second signal required for full T-cell activation. CD28 signaling activates PI3K, AKT, and NF-kappaB pathways, promoting T-cell survival, proliferation, and cytokine production. CTLA-4 competes with CD28 for the same ligands with higher affinity, providing a natural immune checkpoint.
Alterations observed in the corpus
- CD28 was identified as a component of the TCR/co-stimulatory immunological synapse upregulated on-therapy in melanoma patients receiving nivolumab (anti-PD-1), as part of a 695-gene set enriched in the genomic-contraction phenotype and the broader pharmacologic on-therapy response. Pathways enriched in this DEG set included PD-1 signaling, CD28 co-stimulation, downstream TCR signaling, IFN-gamma, and IL-2 signaling (q < 0.10). PMID:29033130
Cancer types (linked)
- SKCM: CD28 upregulation on-therapy was observed in melanoma patients receiving nivolumab, particularly in the genomic-contraction subset with superior clinical benefit. The CD28 co-stimulation pathway was among the most enriched in responder-associated transcriptional changes. PMID:29033130
Co-occurrence and mutual exclusivity
Therapeutic relevance
- The on-therapy enrichment of the CD28 co-stimulation pathway under nivolumab supports the rationale for combination strategies targeting both CD28-CTLA4 axis and PD-1/PD-L1. Anti-CTLA-4 therapy (ipilimumab) blocks the competitive inhibitor of CD28, effectively enhancing CD28 co-stimulatory signaling. PMID:29033130
Open questions
- Whether pre-therapy CD28 expression level predicts ipilimumab-naive vs ipilimumab-progressed patient outcomes on nivolumab was not specifically reported in this study. PMID:29033130
Sources
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