T-cell response to p53 tumor-associated antigen in patients with colorectal carcinoma.
Despite the radical surgical resection performed in patients with colorectal carcinoma, there is a high rate of tumor recurrence. Over an observation period of 3 years, 18% of the patients in our collective suffered a tumor relapse with local or distinct metastases after initial R0-resection. Some evidence suggests that this may be due to suppression of anti-tumor responses, a phenomenon that might be attributed to regulatory T cells. The aim of our study was to investigate the tumor-specific immune response depending on the UICC stage of patients with colorectal cancer. The cellular immune responses against defined antigens that are overexpressed in most of the patients with colorectal cancer were characterized. For this purpose, the tumor suppressor gene, p53, was chosen as the tumor-associated antigen that exhibits mutations and overexpression in up to 60% of colorectal carcinoma. We observed that p53 induced both IFN-gamma and IL-10 secretion. The predominance of IL-10 production indicated that regulatory T cells directly participate in modulating the anti-tumor immune response. IL-10 levels in the blood as well as the expression of regulatory T-cell specific genes at the tumor site correlate with the UICC stage of the disease. These results may provide an explanation for the poor prognosis and increased recurrence rate in patients with advanced carcinoma.
Bueter
Marco
M
Department of Surgery I, University of Wuerzburg, D-97080 Wuerzburg, Germany.
Gasser
Martin
M
Schramm
Nicolai
N
Lebedeva
Tatiana
T
Tocco
Georges
G
Gerstlauer
Christiane
C
Grimm
Martin
M
Nichiporuk
Ekaterina
E
Thalheimer
Andreas
A
Thiede
Arnulf
A
Meyer
Detlef
D
Benichou
Gilles
G
Waaga-Gasser
Ana Maria
AM
D000912:Antibodies, Neoplasm / Q000097:blood*; D015704:CD4 Antigens / Q000235:genetics; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D018604:Epitope Mapping; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009367:Neoplasm Staging; D017354:Point Mutation; D012333:RNA, Messenger / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D000912:Antibodies, Neoplasm; D015704:CD4 Antigens; D050990:GATA3 Transcription Factor; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D016753:Interleukin-10; D007371:Interferon-gamma