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 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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
These findings suggest that OX-40+ CD4+ T cells isolated from tumors and their adjacent draining nodes may represent a tumor-specific population of activated T cells capable of mediating tumor reactivity. These cells may play an exploitable role in future trials of immunotherapy.
Vetto
J T
JT
Department of Surgery, Oregon Health Sciences University, Portland Veterans Affairs Medical Center, 97201-3098, USA.
Lum
S
S
Morris
A
A
Sicotte
M
M
Davis
J
J
Lemon
M
M
Weinberg
A
A
D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000556:secondary; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000737:chemistry* / Q000276:immunology; D008207:Lymphatic Metastasis; D008214:Lymphocytes / Q000737:chemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry*; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D008562:Membrane Glycoproteins / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis*
D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7