Nasrollah Erfani; Mahboobeh Hamedi-Shahraki; Somayeh Rezaeifard; Mohammadreza Haghshenas; Manoochehr Rasouli; Alamtaj Samsami Dehaghani
Volume 11, Issue 2 , June 2014, , Pages 105-112
Abstract
Background: Ovarian cancer is the fifth leading cause of death from malignancy in women. CD4 +CD25+FoxP3+ regulatory T (Treg) cells are a subset of T lymphocytes with great inhibitory impact on immune response. Objectives: To investigate the percentage of CD4 +CD25+FoxP3+ regulatory T cells in the peripheral ...
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Background: Ovarian cancer is the fifth leading cause of death from malignancy in women. CD4 +CD25+FoxP3+ regulatory T (Treg) cells are a subset of T lymphocytes with great inhibitory impact on immune response. Objectives: To investigate the percentage of CD4 +CD25+FoxP3+ regulatory T cells in the peripheral blood of the Iranian patients with epithelial ovarian cancer compared to healthy women and to evaluate the correlation of the Treg cell percentage with clinicopathological characteristics including cancer stage and CA-125 serum level. Methods: Seventeen women with epithelial ovarian cancer and 20 healthy subjects were enrolled in the study. Peripheral blood mononuclear cells were stained at the surface, for CD4 and CD25 molecules, followed by fixation, permeabilization and intracellular staining for FoxP3 molecule. After processing and flowcytometry analysis, prevalence of Treg cells was determined as the percentages of CD25 +FoxP3+ cells among CD4+ lymphocytes. Results: Despite no difference in the percentage of total CD4+ lymphocytes, analysis indicated that Treg cell percentage was significantly higher in ovarian cancer patients than controls (5.7 ± 3.1% versus 2.8 ± 1.4%, p=0.002). A trend toward higher Treg cells was observed in higher stages of ovarian cancer (III+IV) in comparison to lower stages (I+II) (6.5 ± 3.2% vs. 4.44 ± 2.7%, p=0.2). Higher percentage of Treg cells was also observed in the patients with high CA125 (CA-125 >100 U/mL) in comparison to those with low CA-125 serum level (CA-125 ≤100 U/mL) although the difference was not significant (6.44 versus 4.18%, p=0.19). Conclusion: Increased frequency of Tregs in ovarian cancer might participate in immune suppression in these patients. The findings collectively suggest the likely impact of Treg cell–targeted immunotherapy in ovarian cancer.
Zahra Faghih; Somayeh Rezaeifard; Akbar Safaei; Abbas Ghaderi; Nasrollah Erfani
Volume 10, Issue 4 , December 2013, , Pages 193-204
Abstract
Background: CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile. Objective: To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer. Methods: ...
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Background: CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile. Objective: To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer. Methods: Single cell suspensions were obtained from TDLNs of 42 patients with breast cancer. Staining of the cell surface markers and intracellular cytokines was performed using appropriate fluorochrome-conjugated antibodies. The data was acquired on a four-color flow cytometer and was analyzed by CellQuestPro software package. The percentages of different CD8+ cell subtypes (Tc1, Tc2 and Tc17) were quantified in CD8+ T lymphocytes. The comparison was made between LN+ versus LN- patients, as well as patients in different clinico-pathological status. Results: The percentage of Tc1, Tc2 and Tc17 subsets were not significantly different between LN+ and LN- patients. Despite no difference in the percentages of Tc1 cells in LN+ patients with infiltrative ductal carcinoma (IDC), the mean expression of IFN-γ by Tc1 cells decreased significantly in comparison to LN- patients. On the other hand, the percentages of Tc2 and Tc17 effector subsets were increased in advanced stages (p=0.018 and p=0.009, respectively). Conclusion: As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages (Tc2 and Tc17) in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-γ by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.
