CD247
Overview
CD247 (CD3 Zeta Chain-Associated Protein) encodes the CD3 zeta chain, a signal-transducing component of the T-cell receptor (TCR) complex. CD247 contains immunoreceptor tyrosine-based activation motifs (ITAMs) in its cytoplasmic tail that are phosphorylated upon TCR engagement, initiating the T-cell activation cascade. In the context of cancer immunotherapy, CD247 expression reflects TCR-complex integrity and T-cell activation capacity in the tumor microenvironment.
Alterations observed in the corpus
- CD247 was upregulated on-therapy (cycle 1 day 29) relative to pre-therapy in melanoma patients treated with nivolumab (anti-PD-1), as part of a 695-gene set enriched in the genomic-contraction phenotype and a broader 475-DEG pharmacologic on-therapy response (q < 0.20). CD247 expression was enriched in pathways including PD-1 signaling, CD28 co-stimulation, downstream TCR signaling, IFN-gamma, and IL-2 signaling. PMID:29033130
Cancer types (linked)
- SKCM: CD247 was identified among TCR/co-stimulatory immunological synapse components upregulated on-therapy in melanoma patients receiving nivolumab, particularly enriched in the genomic-contraction subset that showed superior clinical benefit. PMID:29033130
Co-occurrence and mutual exclusivity
Therapeutic relevance
- On-therapy upregulation of CD247 and the broader TCR-signaling gene set under nivolumab supports the mechanistic model that anti-PD-1 therapy restores productive T-cell activation in the tumor microenvironment. The contraction-phenotype DEG set stratified survival in independent immunotherapy cohorts. PMID:29033130
Open questions
- Whether baseline CD247 expression level predicts response to anti-PD-1 therapy, independent of on-therapy changes, was not directly assessed in this study. PMID:29033130
Sources
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