Regulatory T Cell as a Target for Cancer Therapy

Abstract

Advances in our understanding of CD4(+)CD25(+)Foxp3(+) regulatory T cells (T(Regs)) enabled the characterization of their activities in maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. Ironically, an effective action of these cells during tumor development can limit beneficial responses by suppressing immunity and limiting antitumor resistance, whereas one of the main functions of the immune system is to eliminate malignant cells. During the last years, the immunological role, mechanism of action, and clinical importance of these cells were profoundly characterized and the relationship between this subset of lymphocytes and cancerous cells arises as a key factor that influences tumor development. Recent insights obtained from clinical studies and experimental mouse models expand our perception of the potential role of T(Regs) in cancer treatment. In this review we describe the basic mechanisms of T(Reg) origin and differentiation, their potential role in cancer, as well as the future perspectives concerning the modulation of these cells as a potential approach for anticancer strategies.

Increased Frequency of CD8+and CD4+Regulatory T Cells in Chronic Lymphocytic Leukemia: Association with Disease Progression

“…Systemic immune dysfunction is a well-known feature of CLL that has already been reported by many investigators, particularly in progressive patients (51,52). As such, immunotherapeutic interventions targeting Treg cells, which have recently been proposed as suitable tool for CLL treatment (53,54), might result in unexpectedly deleterious results, leading to a more aggressive disease. These important immunoregulatory issues should be seriously taken into consideration before any Treg-mediated therapeutic interventions.…”

Tumor-Infiltrating FoxP3+ Tregs and CD8+ T Cells Affect the Prognosis of Hepatocellular Carcinoma Patients

“…Our results further support the conclusions of other authors that tumor-infiltrating Tregs can predict the prognosis of HCC patients [20,46] . Thus, high-density intratumoral Tregs create a generalized immunosuppressive microenvironment and contribute to tumor cells escaping immune surveillance [47]. With the function of immunosuppression, Tregs infiltration plays an important role in tumor progression and clinical behavior by modifying the host immune response.…”

Depletion of regulatory T cells by targeting CC chemokine receptor type 4 with mogamulizumab

“…Eliminating and inhibiting Treg cells to boost host antitumor immunity has long been attempted in studies targeting CD25, CTLA-4, and/or PD-1/PD-L1. 6,7 However, successful elimination of Treg cells may unleash undesirable severe autoimmunity. Studies have found that CCR4 is expressed mainly on effector Treg cells, but not on na€ ıve Treg cells which may differentiate into effector Treg cells.…”