Induced and natural regulatory T cells in human cancer.
ABSTRACT Introduction: Evidence suggests that FOXP3(+)CD25(high)CD4(+) regulatory T cells (Treg) which accumulate in cancer may have beneficial or unfavorable effects on prognosis. The presence in tumor-associated inflammatory infiltrates of two subsets of Treg with distinct phenotypic and functional profiles might explain these conflicting observations. Areas covered: Human inducible (i) Treg arising by tumor-driven conversion of conventional CD4(+) T cells are highly suppressive, therapy-resistant Treg which down-regulate anti-tumor immune responses, promoting tumor growth. Natural (n) Treg, normally responsible for maintaining peripheral tolerance, control cancer-associated inflammation, which favors tumor progression. This division of labor between nTreg and iTreg is not absolute, and overlap may be common. Nevertheless, iTreg play a critical and major role in cancer and cancer therapy. The tumor microenvironment determines the type, frequency and suppression levels of accumulating Treg. Expert opinion: In cancer, a selective removal or silencing of iTreg and not of nTreg should be a therapeutic goal. However, the implementation of this challenging strategy requires further studies of cellular and molecular crosstalk among immune cells in the tumor microenvironment.
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ABSTRACT: The infiltration of regulatory T cells (Tregs) in lymphomas is associated with better prognosis for some types of lymphomas, but knowledge of their role in posttransplant lymphoproliferative disorders (PTLDs) is limited. We therefore investigated the association between the expression of the Treg marker forkhead box protein 3 (FoxP3) in biopsies of PTLDs and survival, PTLD subtype, and clinical characteristics.Transplantation 09/2014; · 3.78 Impact Factor
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ABSTRACT: Although neoadjuvant chemotherapy (NACT) has been increasingly used to improve the outcome of advanced gastric cancer (GC) for decades, its precise efficacy has been difficult to evaluate yet. Abundant studies have investigated the predictive factors that represent the effect of NACT on advanced GC. In the present study, the intratumoral infiltration of regulatory T cells (Tregs) and dendritic cells (DCs) response to NACT in advanced GC and their correlation with prognosis were evaluated. Infiltration of Tregs (marked by Foxp3) and DCs (marked by S-100) in 102 advanced GC specimens with or without NACT was measured using immunohistochemical method. Intratumoral infiltration of Foxp3 Tregs was significantly lower and DC density was significantly higher in NACT group than that in nNACT group (P=0.007, P=0.002, respectively). Infiltration of Foxp3 Tregs was significantly associated with tumor invasion depth (P<0.001). The DC density was significantly correlated with histopathologic type (P=0.035), invasion depth (P=0.002), TNM stage (P=0.018), and lymph node metastasis (P<0.001). There was no significant difference of patient's OS between NACT and nNACT groups (P=0.452); however, patients treated with NACT had longer OS with lower infiltration of Foxp3 Tregs (P<0.001) and higher infiltration of DCs (P=0.010). Univariate and multivariate analyses indicated that infiltration of Foxp3 Tregs and DCs were independent prognostic factors (P=0.002, P=0.003, respectively). The results demonstrated that NACT could decrease intratumoral Foxp3 Tregs infiltration and increase DCs density, and that infiltration of Foxp3 Tregs and DCs may serve as novel prognostic biomarkers of human GC.International journal of clinical and experimental pathology. 01/2014; 7(8):4685-94.
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ABSTRACT: The evolutionally conserved transforming growth factor β (TGFβ) affects multiple cell types in the immune system by either stimulating or inhibiting their differentiation and function. Studies using transgenic mice with ablation of TGFβ or its receptor have revealed the biological significance of TGFβ signaling in the control of T cells. However, it is now clear that TGFβ is more than an immunosuppressive cytokine. Disruption of TGFβ signaling pathway also leads to impaired generation of certain T cell populations. Therefore, in the normal physiological state, TGFβ actively maintains T cell homeostasis and regulates T cell function. However, in the tumor microenvironment, TGFβ creates an immunosuppressive milieu that inhibits antitumor immunity. Here, we review recent advances in our understanding of the roles of TGFβ in the regulation of T cells and tumor immunity.Cytokine & Growth Factor Reviews. 01/2014;