PRESENCE OF THE T-CELL ACTIVATION MARKER OX-40 ON TUMOR-INFILTRATING LYMPHOCYTES AND DRAINING LYMPH-NODE CELLS FROM PATIENTS WITH MELANOMA AND HEAD AND NECK CANCERS

BACKGROUND: The OX-40 antigen is a cell surface glycoprotein in the tu mor necrosis factor receptor family that is expressed primarily on act ivated CD4+ T cells, Selective target organ expression of the OX-40 re ceptor on autoantigen specific T cells has been found in autoimmune di sease, In order to evaluate whether OX-40 is expressed on T cells from patients with nodal-draining carcinomas, OX-40 expression was assesse d in tumor infiltrating lymphocytes (TILs), draining lymph node cells (DLNCs), and/or peripheral blood lymphocytes (PBLs) of 13 patients wit h head and neck squamous cell carcinomas and 9 patients with melanomas . METHODS: Cell phenotype was determined by fluorescence cell analysis using a monoclonal anti-body to human OX-40, and CD4+ T cell lymphoki ne production was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Expression of the OX-40 receptor was foun d in as many as 31% of the TILs and as many as 28% of the DLNCs tested , Conversely, no OX-40 expression was found in PBLs, In addition, CD4 T cells isolated from DLNCs (but not from TILs or PBLs) secreted a Th 1 pattern of cytokines (IL-2, gamma interferon), Go-culture of autolog ous CD4+ TILs with an MHC class II+ melanoma cell line transfected wit h OX-40 ligand cDNA resulted in T cell proliferation and in vitro tumo r regression, CONCLUSIONS: These findings suggest that OX-40+ CD4+ T c ells isolated from tumors and their adjacent draining nodes may repres ent a tumor-specific population of activated T cells capable of mediat ing tumor reactivity, These cells may play an exploitable role in futu re trials of immunotherapy, (C) 1997 by Excerpta Medica, Inc.