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

• Published in: The American journal of surgery 1997-09, Vol.174 (3), p.258-265
• Main Authors: Vetto, John T., Lum, Sharon, Morris, Arden, Sicotte, Mary, Davis, Jennifer, Lemon, Michael, Weinberg, Andrew
• Format: Article
• Language: English
• Subjects: Antigens; Autoimmune diseases; Biological and medical sciences; Cancer; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - secondary; CD4 antigen; CD4-Positive T-Lymphocytes - chemistry; Cell activation; Cell culture; Cell proliferation; Cell surface; Clinical trials; Dermatology; Fluorescence; Glycoproteins; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - pathology; Humans; Immunotherapy; Interleukin 2; Lymph nodes; Lymph Nodes - chemistry; Lymph Nodes - immunology; Lymphatic Metastasis; Lymphatic system; Lymphocytes; Lymphocytes - chemistry; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - chemistry; Major histocompatibility complex; Medical sciences; Melanoma; Melanoma - immunology; Melanoma - secondary; Membrane Glycoproteins - analysis; Monoclonal antibodies; Peripheral blood; Phenotypes; Polymerase chain reaction; Receptors; Receptors, Immunologic - analysis; Receptors, OX40; Receptors, Tumor Necrosis Factor; RNA-directed DNA polymerase; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Squamous cell carcinoma; Tumor Necrosis Factor Receptor Superfamily, Member 7 - analysis; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; γ-Interferon
• ISSN: 0002-9610; 1879-1883
• DOI: 10.1016/S0002-9610(97)00139-6

The OX-40 antigen is a cell surface glycoprotein in the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells. Selective target organ expression of the OX-40 receptor on autoantigen specific T cells has been found in autoimmune disease. In order to evaluate whether OX-40 is expressed on T cells from patients with nodal-draining carcinomas, OX-40 expression was assessed in tumor infiltrating lymphocytes (TILs), draining lymph node cells (DLNCs), and/or peripheral blood lymphocytes (PBLs) of 13 patients with head and neck squamous cell carcinomas and 9 patients with melanomas. Cell phenotype was determined by fluorescence cell analysis using a monoclonal antibody to human OX-40, and CD4+ T cell lymphokine production was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of the OX-40 receptor was found 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 Th1 pattern of cytokines (IL-2, gamma Interferon). Co-culture of autologous CD4+ TILs with an MHC class II+ melanoma cell line transfected with OX-40 ligand cDNA resulted in T cell proliferation and in vitro tumor regression. These findings suggest that OX-40+ CD4+ T cells isolated from tumors and their adjacent draining nodes may represent a tumorspecific population of activated T cells capable of mediating tumor reactivity. These cells may play an exploitable role in future trials of immunotherapy.