Immunohistologic responses within dermal metastatic melanoma lesions of patients treated with a synthetic peptide vaccine

Three patients with dermal metastatic melanoma lesions responding to a synt hetic peptide vaccine (g209-2M) derived from the sequence of gp100 melanoma associated antigen, along with either IL-2 or granulocyte-monocyte colony- stimulating factor were studied to characterize the immunologic response oc curring within and around the lesions during therapy. Standard immunocytoch emical techniques were used to study the T-cell response (CD3, CD4, and CD8 ), the B-cell response (CD20), and the expression of class II major histoco mpatibility complex (HLA-DR) antigens. Between 40 and 65 days after the ini tiation of vaccine therapy (more than 3 weeks after the second dose of vacc ine), the gross tumor size decreased and the tumors from all three patients showed substantial histologic regression associated with increased number rs of tumor-infiltrating, lymphocytes and melanophages. The increased lesio nal tumor-infiltrating lymphocytes consisted of CD3(+) T cells and very few CD20(+) B cells. In two of the three patients, the T-cell infiltrate occur ring during the initial tumor regression consisted predominantly of CD8(+) cells. The number of perivascular T cells surrounding small vessels adjacen t to melanoma lesions also increased during the time of peak histologic tum or regression. Also during the course of vaccine therapy, the expression of HLA-DR by vascular endothelial cells of the small vessels adjacent to lesi ons increased in all three patients, and elevated endothelial expression of HLA-DR was maintained in two of the three patients. These results show tha t patients with metastatic melanoma, who responded to melanoma vaccine ther apy, had a predominantly CD8(+) T-cell infiltrate associated with a loss of tumor cells. As the tumor cells diminished, they were replaced by heavily pigmented melanophages.