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.
Fritsch
M
M
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rosenberg
S A
SA
Duray
P H
PH
D000328:Adult; D000951:Antigens, Neoplasm / Q000032:analysis*; D001707:Biopsy, Needle; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D019496:Cancer Vaccines / Q000008:administration & dosage*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D011379:Prognosis; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000473:pathology* / Q000628:therapy*; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D019496:Cancer Vaccines; D006684:HLA-DR Antigens