TY - JOUR
T1 - Immunohistologic Responses Within Dermal Metastatic Melanoma Lesions of Patients Treated With a Synthetic Peptide Vaccine
AU - Fritsch, M.
AU - Rosenberg, S. A.
AU - Duray, P. H.
PY - 2000/1/1
Y1 - 2000/1/1
N2 - 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.
AB - 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.
KW - CD8 T-cell infiltrate
KW - Melanoma
KW - Synthetic peptide vaccine
UR - http://www.scopus.com/inward/record.url?scp=0033867286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033867286&partnerID=8YFLogxK
U2 - 10.1097/00002371-200009000-00006
DO - 10.1097/00002371-200009000-00006
M3 - Article
C2 - 11001549
AN - SCOPUS:0033867286
SN - 1524-9557
VL - 23
SP - 557
EP - 569
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
IS - 5
ER -