Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis | Schaefer et al. Journal of Translational Medicine 2010 8 79 http content 8 1 79 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Dynamic changes in cellular infiltrates with repeated cutaneous vaccination a histologic and immunophenotypic analysis Jochen T Schaefer 2 3 4 James W Patterson 2 3 4 Donna H Deacon 1 2 Mark E Smolkin5 Gina R Petroni 5 Emily M Jackson 2 Craig L Slingluff Jr1 2 Abstract Background Melanoma vaccines have not been optimized. Adjuvants are added to activate dendritic cells DCs and to induce a favourable immunologic milieu however little is known about their cellular and molecular effects in human skin. We hypothesized that a vaccine in incomplete Freund s adjuvant IFA would increase dermal Th1 and Tc1-lymphocytes and mature DCs but that repeated vaccination may increase regulatory cells. Methods During and after 6 weekly immunizations with a multipeptide vaccine immunization sites were biopsied at weeks 0 1 3 7 or 12. In 36 participants we enumerated DCs and lymphocyte subsets by immunohistochemistry and characterized their location within skin compartments. Results Mature DCs aggregated with lymphocytes around superficial vessels however immature DCs were randomly distributed. Over time there was no change in mature DCs. Increases in T and B-cells were noted. Th2 cells outnumbered Th1 lymphocytes after 1 vaccine 1. Eosinophils and FoxP3 cells accumulated especially after 3 vaccinations the former cell population most abundantly in deeper layers. Conclusions A multipeptide IFA vaccine may induce a Th2-dominant microenvironment which is reversed with repeat vaccination. However repeat vaccination may increase FoxP3 T-cells and eosinophils. These data suggest multiple opportunities to optimize vaccine regimens and potential endpoints for monitoring the effects of new adjuvants. Trail Registration Identifier NCT00705640 Background Existing therapies for advanced melanoma are rarely .
