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


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.
Zelle-Rieser
C
C
Department of Urology, University of Innsbruck, Innsbruck, Austria.
Barsoum
A L
AL
Sallusto
F
F
Ramoner
R
R
Rohrer
J W
JW
Höltl
L
L
Bartsch
G
G
Coggin JH
J R
JR
Thurnher
M
M
D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007167:Immunotherapy; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology; D011498:Protein Precursors / Q000032:analysis* / Q000276:immunology*; D017474:Receptors, Laminin
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D011498:Protein Precursors; D017474:Receptors, Laminin; C031192:oncofetal antigens; D016753:Interleukin-10; D007371:Interferon-gamma