Autologous melanoma vaccine induces inflammatory responses in melanoma metastases: relevance to immunologic regression and immunotherapy.
Human primary malignant melanoma is often accompanied by a host response of infiltrating lymphocytes suggestive of tumor antigen-induced immunity and correlated in some tumors with prognosis. Whereas metastatic melanoma deposits typically are not inflamed and contain relatively few lymphocytes and dendritic immune cells, immunization with autologous melanoma-cell vaccine may induce a clinical inflammatory response associated with mononuclear-cell infiltration. In this study, we characterize immune responses to dermal and subcutaneous melanoma metastases in dinitrophenyl (DNP)-pre-sensitized patients immunized with DNP-conjugated melanoma cells. Patients so treated develop cutaneous delayed hypersensitivity responses to DNP-conjugated autologous mononuclear cells, and approximately one-half show clinical evidence of inflammation and regression of metastases within 2-4 months. Whereas pre-vaccination biopsies of metastatic melanoma failed to reveal significant infiltration by lymphocytes, biopsies obtained after vaccination and coincident with clinical inflammation were markedly infiltrated preponderantly by T cells with a CD8+ phenotype. Clustering of these cells about individual degenerating melanoma cells in a manner analogous to "satellitosis" was a consistent feature of this reaction. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen (HLA)-DR by melanoma cells were invariably associated with zones of T-cell infiltration, whereas diminished or absent expression was observed in relatively unaffected regions of tumors. Numerous HLA-DR+, CD4+, CD1-, Leu-1- dendritic cells were also associated with zones of early T-cell infiltration. These data indicate that clinical inflammation and regression of metastatic melanoma induced by autologous melanoma-cell vaccine involves activated T cells with cytotoxic-suppressor phenotype and dendritic cells putatively capable of local antigen presentation. ICAM-1 upregulation on melanoma cells is a likely mediator of ligand interaction between infiltrating T cells and target cells in this model of antigen-induced host anti-tumor response. Structural alterations identified in this setting (e.g., tumor cell satellitosis) may provide additional insight into identifying features of naturally occurring host immune responses to primary cutaneous melanomas.
Murphy
G F
GF
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia.
Radu
A
A
Kaminer
M
M
Berd
D
D
D003876:Dermatitis, Atopic / Q000209:etiology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007167:Immunotherapy; D007249:Inflammation / Q000209:etiology*; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating; D008545:Melanoma / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D012878:Skin Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D013997:Time Factors; D014612:Vaccines / Q000009:adverse effects
D014612:Vaccines