Phase-resolved transcriptomic bottlenecks in peptide cancer vaccine response
Background: Peptide cancer vaccines can elicit antigen-specific immunity, but peripheral immunogenicity often does not translate into durable tumor control. Methods: We analyzed transcriptomic profiles across three public human peptide-vaccine cohorts: C1/GSE278476, a MUC1 plus Poly-ICLC PBMC RNA-seq cohort with ordered anti-MUC1 IgG response classes; C2/GSE85698, manufactured dendritic-cell…
Peptide cancer vaccines have shown promise in eliciting antigen-specific immunity, yet their ability to translate into long-lasting tumor control remains limited. To better understand the underlying mechanisms, researchers conducted a comprehensive analysis of transcriptomic profiles across three public human peptide-vaccine cohorts: C1/GSE278476, C2/GSE85698, and C3/GSE53922.
The study focused on specific gene modules and utilized mean standardized scores to assess their impact on vaccine response. In cohort C1, baseline immune-readiness demonstrated a favorable pattern, with a positive association (beta=0.301, p=0.0072) and longer survival in cohort C3 (HR=0.662, 95% CI 0.532-0.823, p=0.000206). However, baseline erythroid/inflammatory drag exhibited an inverse relationship in C1 (beta=-0.258, p=0.031), which was linked to inferior survival in C3 (HR=1.390, 95% CI 1.181-1.636, p=0.0000755).
Moving on to cohort C2, the analysis revealed lower tolerogenic/myeloid dendritic-cell product-state expression in strong ELISpot responders (8/19 focused genes, q-values). These findings suggest that the transcriptomic landscape plays a crucial role in determining the effectiveness of peptide cancer vaccines and could inform future strategies to improve vaccine response and patient outcomes.
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