Autologous Melanoma Vaccine Induces Inflammatory Responses in Melanoma Metastases: Relevance to Immunologic Regression and Immunotherapy

George F. Murphy, Antoaneta Radu, Michael Kaminer, David Berd
1993 Journal of Investigative Dermatology  
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 mononuclearcell infiltration. In this study, we characterize
more » ... ne 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 þ 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 þ , CD4 þ , CD1 À , Leu-1 À 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 antitumor 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.
doi:10.1038/jid.1993.59 fatcat:s3ig4aessfhwxosoxi3gkitiza