Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Immune cell transcriptional profiles from pre-vaccination peripheral blood predict immune response to preventative MUC1 cancer vaccine.

Abstract

BACKGROUND: Recent advances in vaccine technology raise hopes for effective cancer preventative vaccines. The first clinical trials (single-arm NCT007773097; double-blind, placebo controlled randomized trial NCT02134925) of a non-viral cancer preventative vaccine were conducted in individuals with previous advanced colonic adenoma to test the safety and immunogenicity of the MUC1 tumor antigen vaccine. The vaccine was safe and strongly immunogenic in 43 %-25 % of participants. The lack of response in a significant number of participants suggested that the pre-malignant immune system may have already been exposed to some level of suppression, something previously reported only in cancer. METHODS: Single-cell RNA-sequencing (scRNA-seq) data were collected from banked pre-vaccination peripheral blood mononuclear cells (PBMCs) (16 immune responders and 16 non-responders) and analyzed using standard bioinformatic and novel machine learning methods. RESULTS: We identified specific cell types, genes, and pathways characteristic of vaccine response. A significantly higher percentage of CD4 + naive T cells and lower percentage of CD8 + T effector memory (TEM) cells and CD16 + monocytes were present in responders. Differential gene expression (DGE) and transcription factor inference analysis showed a higher level of expression of T cell activation genes (like Fos, Jun) in CD4 + naive T cells. Pathway analysis showed enriched signaling activity in responders. Furthermore, Bayesian graph analysis suggested that these genes were mechanistically related to response. CONCLUSIONS: Our analyses identified several immune mechanisms and candidate biomarkers which can be further validated as predictors of immune responses to a preventative cancer vaccine. These could facilitate selection of individuals likely to benefit from a vaccine or be used in further research to improve vaccine responses.