The significance of Treg cells in defective tumor immunity

Abstract

Regulatory T cells (Treg) enriched in FoxP3+, glucocorticoid-induced TNF receptor+, and cytotoxic T-lymphocyte-associated antigen-4+ exert a potential to suppress effector T cells in the periphery. These cells exist in markedly higher proportions within tumor-infiltrating lymphocytes, peripheral blood lymphocytes, and/or regional lymph node lymphocytes of patients with cancer and their frequencies are suggested to be strongly related to tumor progression and inversely correlated with the efficacy of treatment. Tumor-specific Treg cells require ligand-specific activation and cell-to-cell contact to exert their suppressive activity on tumor-specific effector cells (CD8+ cytotoxic T lymphocytes and CD4+ Th cells), which includes decreased cytotoxity, proliferation, and Th1 cytokine secrection. Depletion or blockade of Treg cells can enhance immune protection from tumor-associated antigens that are expressed as self antigens. Recent studies revealed that lymphoma T cells might adopt a Treg profile as well. Studies assessing the influence of chemotherapy on Treg cells have also been included in this review.

Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma

“…Generally, these cells exist in markedly higher proportions within TILs, PBLs, and/or regional lymph node lymphocytes of cancer patients, and their frequencies are suggested to be strongly related to tumor progression and inversely correlated with the efficacy of treatment. 24 Our study showed that the high prevalence of regulatory T cells in the cancer stroma as well as the peripheral blood of EC patients was closely correlated with clinically malignant features, including tumor grade, stage, lymph node metastasis, and myometrium invasion. The prevalence of regulatory T cells in TILs within the cancer milieu can be a positive indicator of tumor aggressiveness.…”

“…Tumor-specific regulatory T cells require ligand-specific activation and cell-to-cell contact to exert their suppressive activity on tumor-specific effector cells (CD8 þ cytotoxic T lymphocytes and CD4 þ Th cells), which includes decreased cytotoxicity, proliferation, and Th1 cytokine secretion. 24 In the present study of TILs, these regulatory T cells may have averted appropriate antitumor immune responses through certain cytolytic enzyme-dependent essential pathways. In our study, granzyme B was scarcely expressed in peripheral regulatory T cells, but was highly expressed in 5% to 30% of CD4 þ CD25 þ regulatory T cells in the tumor microenvironment.…”

An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer

“…However, autoreactive T cells that migrate into the tumour periphery are controlled by a number of peripheral mechanisms including the induction of regulatory/suppressor T cells [8]. CD4 + T regulatory (T reg) cells include at least four populations that differ in phenotype, cytokine secretion profile, and suppressive mechanisms [9,10]. One prevailing phenotype is the naturally occurring T reg cells that originate in the thymus and are involved in protection from autoimmune responses.…”

“…These cells naturally arise in the thymus and after differentiation, the naïve CD4 + CD25 + CD45RA + T cells are exported to the periphery where they suppress the activation of T cells potentially reactive to the self [10]. In addition to CD4 and CD25 markers, T reg also constitutively express CD45RO and CD152…”

Anti-4-1BB scFv immunogene therapy and low dose cyclophosphamide exhibit a synergistic antitumor effect in established murine lung tumors

“…A heavier localized inflammatory cell infiltration was observed in TC-1 Treg cells are effective inhibitors of immune responses to tumor antigens and have been reported to be more prevalent in the blood and tumor microenvironment of cancer patients. 31,32 Thus, methods of decreasing the number of Treg cells or inhibiting their function are considered valuable for cancer immunotherapy. There are three main approaches currently used to decrease the impact of Treg cells: low dose CTX; 33 PC61 (a specific antibody directed against the IL-2 receptor on Tregs); 34 and denileukin diftitox (DD, a fusion protein designed to have a direct cytocidal action on cells which express the IL-2 receptor).…”