Augmentation of regulatory T cells (CD4+CD25+Foxp3+) correlates with tumor stage in patients with colorectal cancer.
Recent evidence suggests that decline of regulatory T cells (Tregs) play a critical role in the prevalence of autoimmune diseases inhibiting the maintenance of peripheral self tolerance, while its augmentation leads to insufficient antitumor response, accompanied with poor prognosis in various malignancies. Increased number of Tregs (CD4+CD25+FoxP3+) were noticed in peripheral blood mononuclear cells (PBMCs), tumor-infiltrating lymphocytes (TILs) and/or regional lymph nodes lymphocytes (LNLs) of patients with gastrointestinal tumors. The aim of our study was to investigate the correlation between the percentage of Tregs in peripheral blood of patients with colorectal carcinoma, using flow cytometric technique and tumor stages, classified as Dukes' A, B, C or D and by stage of differentiation. Peripheral blood venous samples were obtained from 92 patients with colorectal cancer and from 30 healthy adult volunteers.


METHODS
Linear regression equations were generated using a least-squares method and analyzed for differences of covariance. Statistical significance was calculated by Mann Whitney U-test. Our data has shown that 15% patients with colorectal cancer were classified as Dukes' A, 41% were Dukes' B, 35% were Dukes' C and 9% were Dukes' D. 54% patients with CRC were well differentiated, 11% were poorly differentiated, 20 were moderately differentiated, tage, 4% were mucinous carcinoma and rest of 11% were partly good differentiated with mucinous components. The increased percentage of Tregs in colorectal cancer patients correlates with tumor stage. These results indicate a possible involvement of regulatory T cells in disease progression. New strategies using inhibition or depletion of Tregs are necessary to elucidate the complexity of defective tumor immunity.
Department of Abdominal Surgery, Rijeka University Hospital Centre, University of Rijeka, School of Medicine, Rijeka, Croatia.
Dordano
D
Bacić
Miljenko
M
Uravić
Roberta
R
Bacić
Ivana
I
Sutić
Neno
N
Petrosić
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D009367:Neoplasm Staging / Q000145:classification / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D015415:Biomarkers; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit