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Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast

Leong, Pooi Pooi and Mohammad, Rohaizak and Ibrahim, Naqiyah and Ithnin, Hairuszah and Abdullah, Maha and Davis, William C and Seow, Heng Fong (2006) Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast. Immunology Letters, 102 (2). pp. 229-236. ISSN 0165-2478

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Abstract

Dysfunction of the host immune system in cancer patients can be due to a number of reasons including suppression of tumour associated antigen reactive lymphocytes by regulatory T (Treg) cells. In this study, we used flow cytometry to determine the phenotype and relative abundance of the tumour infiltrating lymphocytes (TILs) from 47 enzymatically dissociated tumour specimens from patients with infiltrating ductal carcinoma (IDC) of the breast. The expression of both effector and regulatory markers on the TILs were determined by using a panel of monoclonal antibodies. Analysis revealed CD8(+) T cells (23.4+/-2.1%) were predominant in TILs, followed by CD4(+) T cells (12.6+/-1.7%) and CD56(+) natural killer cells (6.4+/-0.7%). The CD4(+)/CD8(+) ratio was 0.8+/-0.9%. Of the CD8(+) cells, there was a higher number (68.4+/-3.5%) that expressed the effector phenotype, namely, CD8(+)CD28(+) and about 46% of this subset expressed the activation marker, CD25. Thus, a lower number of infiltrating CD8(+) T cells (31.6+/-2.8%) expressed the marker for the suppressor phenotype, CD8(+)CD28(-). Of the CD4(+) T cells, 59.6+/-3.9% expressed the marker for the regulatory phenotype, CD4(+)CD25(+). About 43.6+/-3.8% CD4(+)CD25(+) subset co-expressed both the CD152 and FOXP3, the Treg-associated molecules. A positive correlation was found between the presence of CD4(+)CD25(+) subset and age (> or =50 years old) (r=0.51; p=0.045). However, no significant correlation between tumour stage and CD4(+)CD25(+) T cells was found. In addition, we also found that the CD4(+)CD25(-) subset correlated with the expression of the nuclear oestrogen receptor (ER)-alpha in the tumour cells (r=0.45; p=0.040). In conclusion, we detected the presence of cells expressing the markers for Tregs (CD4(+)CD25(+)) and suppressor (CD8(+)CD28(-)) in the tumour microenvironment. This is the first report of the relative abundance of Treg co-expressing CD152 and FOXP3 in breast carcinoma.

Item Type: Article
Uncontrolled Keywords: ResPubID16883, cancer, tumour infiltrating lymphocytes, regulatory, effector, four-colour analysis
Subjects: Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
FOR Classification > 1112 Oncology and Carcinogenesis
SEO Classification > 970111 Expanding Knowledge in the Medical and Health Sciences
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Depositing User: VUIR
Date Deposited: 19 Aug 2011 00:34
Last Modified: 19 Aug 2011 00:34
URI: http://vuir.vu.edu.au/id/eprint/3027
DOI: 10.1016/j.imlet.2005.09.006
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Citations in Scopus: 31 - View on Scopus

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