Skin biopsies in DC vaccines for stage III-IV melanoma patients: role of neutrophils?

Abstract

Dendritic cell (DC) vaccines are used for the induction of anti-tumor T cell reaction in melanoma patients. DC are generated in vitro, pulsed with antigen and matured prior to injection. They are supposed to migrate to lymph nodes and to present the processed antigen to naive T cells allowing activation of tumor-specific lymphocytes. It has been suggested that intradermal injection allows a superior migration to the lymph node. Eight HLA-A2 positive patients with stage III or IV melanomas expressing NA 17 antigen were collected. They were included in a pilot trial of vaccination in which they received IL3/INFb DC presenting the NA17 A2 antigen. In each patient, a skin biopsy was performed at the injection site, 24 h after inoculation. The striking features of the biopsies were the presence of a perivascular CD3+/CD8+ T cell infiltrate with a slight population of CD4+ cells and the presence of a massive neutrophilic infiltrate associated with the injected DC still present, realizing a suppurative granuloma. The persistence of DC 24 h after the injection suggests that migration in the lymph node is not necessary for the induction of the immune response. The skin itself could be the location of a reaction starting with a massive recruitment of neutrophils.