Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma

J Urol. 2001 May;165(5):1705-9.

Abstract

Purpose: The 32 to 44 kDa. oncofetal antigen-immature laminin receptor (OFA-iLR) is a multifunctional protein expressed by various tumors, including breast, lung, ovary and prostate carcinoma as well as lymphoma. OFA-iLR has been implicated in tumor invasiveness, metastasis and growth. Interferon-gamma producing effector T cells and interleukin (IL)-10 producing suppressor T cells specific for OFA-iLR have been described.

Materials and methods: The 43515 IgG2a anti-OFA-iLR monoclonal antibody was used to detect OFA-iLR expression in human renal cell carcinoma tissue by flow cytometry and immunoblotting. Spontaneous or therapy induced immune responses against OFA-iLR were determined in patients with metastatic renal cell carcinoma. Proliferative and cytokine (interferon-gamma and IL-10) responses of peripheral blood mononuclear cells from patients with renal cell carcinoma against recombinant OFA-iLR were assessed.

Results: Using flow cytometry OFA-iLR was detected in all 13 tumors tested. Immunoblotting revealed differences in OFA-iLR expression in renal cell carcinoma and normal kidney tissue. OFA-iLR specific proliferative and cytokine responses of mononuclear cells were detected in all 6 patients tested. Importantly evidence was also obtained that treating metastatic renal cell carcinoma with tumor lysate pulsed dendritic cells would enhance OFA-iLR specific immunity.

Conclusions: This study demonstrates that OFA-iLR is an immunogenic tumor associated antigen in human renal cell carcinoma. OFA-iLR specific effector T cells producing interferon-gamma may have a role in the control of tumor growth, whereas suppressor T cells producing IL-10 may promote tumor tolerance and, thus, tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / analysis*
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / administration & dosage
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / therapy
  • Cell Division
  • Dendritic Cells / immunology
  • Flow Cytometry
  • Humans
  • Immunoblotting
  • Immunotherapy
  • In Vitro Techniques
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Kidney / metabolism
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / therapy
  • Leukocytes, Mononuclear / immunology
  • Protein Precursors / analysis*
  • Protein Precursors / immunology*
  • Receptors, Laminin*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Protein Precursors
  • Receptors, Laminin
  • oncofetal antigens
  • Interleukin-10
  • Interferon-gamma