2). The data imply that radiotherapy upregulates the expression of Akt in the Tregs of BCa. A portion of the isolated cells in Fig. 1 was analysed by flow cytometry for the frequency of apoptotic Tregs. The results showed that much less frequency of apoptotic Tregs was detected in RA group than in the

nRA group (Fig. 3). The results implicate that radiation promotes the Treg survival in the cancer that may be via preventing the apoptotic activities in the Tregs. To further investigate the mechanism by which radiation promotes the survival of Tregs in BCa tissue, we generated CD4+ CD25+ Foxp3+ Tregs from human peripheral mononuclear cells. After treated with radiation (RA group), the levels of Akt were markedly increased in activated Tregs in a radiation dose-dependent manner. The frequency of apoptotic Tregs was also less among the Tregs of RA group than nRA group; the latter Cabozantinib mouse was activated, but not treated with radiation. Considering the increase in Akt might protect the Tregs from becoming apoptosis during radiation, some cells were treated with Akt inhibitor during the activation and radiation. Indeed, the frequency of apoptotic Tregs in RA group was similar to that of the nRA group (Fig. 4). The results indicate that RA can significantly increase the expression of Akt in Tregs that efficiently prevents Tregs to be apoptotic. This study revealed a side effect of radiotherapy

in the treatment for BCa. After radiation, MK-2206 supplier the frequency of the tumour infiltration Tregs significantly

increased in the BCa tissue. The levels of Akt were increased in the Tregs, which suppressed the sensitivity to apoptosis in Tregs. The tumour-infiltrating T cells play an important role in tumour growth. CD8+ T cells can inhibit ID-8 tumour growth by inducing tumour cell death or apoptosis. However, Tregs can inhibit CD8+ T cells in the tumour tissue that facilitates the tumour survival. Kaycer et al. [11] analysed a group of tumour-infiltrating T lymphocytes in non-small cell lung cancer and found that high numbers of Tregs were of beneficial prognostic influence in patients with non-small cell lung cancer. Boorjian et al. [12] observed a group of patients with liver cancer and found that the high frequency of Tregs in the tumour tissue was correlated with poor survival rate of the patients. Thus, to elucidate the causative factors increasing Tregs in tumour tissue is of significance. Yang et al. [13] found that colorectal cancer expressed high levels of integrin alpha versus beta 6, which had positive correlation with the frequency of Tregs in the tumour tissue. Our data have contributed one more novel evidence that radiotherapy also favours the increase in Treg in Bca tissue. Radiotherapy is an important therapeutic remedy in the treatment for malignant tumours. Because of its side effects, high doses of radiation should be avoided.