PMID- 8440919 OWN - NLM STAT- MEDLINE DCOM- 19930401 LR - 20190723 IS - 0022-202X (Print) IS - 0022-202X (Linking) VI - 100 IP - 3 DP - 1993 Mar TI - Autologous melanoma vaccine induces inflammatory responses in melanoma metastases: relevance to immunologic regression and immunotherapy. PG - 335S-341S AB - 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. FAU - Murphy, G F AU - Murphy GF AD - Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia. FAU - Radu, A AU - Radu A FAU - Kaminer, M AU - Kaminer M FAU - Berd, D AU - Berd D LA - eng GR - CA-39248/CA/NCI NIH HHS/United States GR - CA-40358/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (Vaccines) SB - IM MH - Dermatitis, Atopic/*etiology MH - Humans MH - Hypersensitivity, Delayed/etiology MH - Immunotherapy MH - Inflammation/*etiology MH - Lymphatic Metastasis MH - Lymphocytes, Tumor-Infiltrating MH - Melanoma/immunology/*secondary/therapy MH - Skin Neoplasms/immunology/*secondary/therapy MH - Time Factors MH - Vaccines/adverse effects EDAT- 1993/03/01 00:00 MHDA- 1993/03/01 00:01 CRDT- 1993/03/01 00:00 PHST- 1993/03/01 00:00 [pubmed] PHST- 1993/03/01 00:01 [medline] PHST- 1993/03/01 00:00 [entrez] AID - 10.1111/1523-1747.ep12470236 [doi] PST - ppublish SO - J Invest Dermatol. 1993 Mar;100(3):335S-341S. doi: 10.1111/1523-1747.ep12470236.