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Journal of Translational Medicine

, 8:79

Immunobiology and immunotherapy

Abstract

BackgroundMelanoma 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.

MethodsDuring 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.

ResultsMature 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 6.6:1. Eosinophils and FoxP3 cells accumulated, especially after 3 vaccinations, the former cell population most abundantly in deeper layers.

ConclusionsA multipeptide-IFA vaccine may induce a Th2-dominant microenvironment, which is reversed with repeat vaccination. However, repeat vaccination may increase FoxP3T-cells and eosinophils. These data suggest multiple opportunities to optimize vaccine regimens and potential endpoints for monitoring the effects of new adjuvants.

Trail RegistrationClinicalTrials.gov Identifier: NCT00705640

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-8-79 contains supplementary material, which is available to authorized users.

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Fuente: https://link.springer.com/







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