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

Am J Surg. 1997 Sep;174(3):258-65. doi: 10.1016/s0002-9610(97)00139-6.


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.

MeSH terms

  • CD4-Positive T-Lymphocytes / chemistry*
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / secondary
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Lymph Nodes / chemistry*
  • Lymph Nodes / immunology
  • Lymphatic Metastasis
  • Lymphocytes / chemistry
  • Lymphocytes, Tumor-Infiltrating / chemistry*
  • Melanoma / immunology*
  • Melanoma / secondary
  • Membrane Glycoproteins / analysis
  • Receptors, Immunologic / analysis*
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor*
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / analysis*


  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • TNFRSF4 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 7