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 synthetic 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 occurring within and around the lesions during therapy. Standard immunocytochemical 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 histocompatibility complex (HLA-DR) antigens. Between 40 and 65 days after the initiation of vaccine therapy (more than 3 weeks after the second dose of vaccine), the gross tumor size decreased and the tumors from all three patients showed substantial histologic regression associated with increased numbers of tumor-infiltrating lymphocytes and melanophages. The increased lesional tumor-infiltrating lymphocytes consisted of CD3⁺ T cells and very few CD20⁺ B cells. In two of the three patients, the T-cell infiltrate occurring during the initial tumor regression consisted predominantly of CD8⁺ cells. The number of perivascular T cells surrounding small vessels adjacent to melanoma lesions also increased during the time of peak histologic tumor regression. Also during the course of vaccine therapy, the expression of HLA-DR by vascular endothelial cells of the small vessels adjacent to lesions increased in all three patients, and elevated endothelial expression of HLA-DR was maintained in two of the three patients. These results show that patients with metastatic melanoma, who responded to melanoma vaccine therapy, 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.