Early biomarkers of efficacy of vaccines are lacking. We hypothesize that intracellular signaling in T cells following administration of the vaccine yields a “fingerprint” predictive of an effective or a tolerogenic immune response and could be used as a biomarker. Our lab has explored immune responses to human tumor MUC1 peptide vaccine in wildtype (WT) versus human MUC1 transgenic mice (MUC1.Tg) and found that they were significantly lower in MUC1Tg. To “fingerprint” signaling differences between the effective immune response in WT versus the lower (tolerogenic) response in MUC1.Tg mice, we vaccinated both with DC loaded with MUC1 peptide, harvested spleens (n=3) at 1,6,12, and 24 hours post vaccination and analyzed phosphorylation downstream of TCR and costimulatory molecules, as well as activation of cell survival, proliferation, and apoptosis signaling cascades. We saw early increases in pSTAT1, pSTAT4, and p38MAPK with a trend towards higher phosphorylation in WT mice that did not reach statistical significance. There was also a trend towards higher phosphorylation in WT mice in pLCK and pAKT downstream of the TCR and costimulatory molecules. Interestingly, at certain timepoints we observed increases in signaling in MUC1.Tg mice, which may serve as compensatory mechanisms that we will further investigate. We are challenging these two vaccinated groups of mice with MUC1+ tumor in an attempt to correlate early T cell activation with later protection from tumor growth.
- Copyright © 2011 by The American Association of Immunologists, Inc.