<p>T-Regulatory Cells In Tumor Progression And Therapy</p>

Abstract

Regulatory T cells (Tregs) are important members of the immune system regulating the host responses to infection and neoplasms. Tregs prevent autoimmune disorders by protecting the host-cells from an immune response, related to the peripheral tolerance. However, tumor cells use Tregs as a shield to protect themselves against anti-tumor immune response. Thus, Tregs are a hurdle in achieving the complete potential of anti-cancer therapies including immunotherapy. This has prompted the development of novel adjuvant therapies that obviate their negative effects thereby enhancing the therapeutic efficacy. Our earlier studies have shown the efficacy of the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG) by reducing the induced Tregs pool and enhance immune stimulation as well as local tumor control. These findings have suggested its potential for enhancing the efficacy of immunotherapy, besides radiotherapy and chemotherapy. This review provides a brief account of the current status of Tregs as a component of the immune-biology of tumors and various preclinical and clinical strategies pursued to obviate the limitations imposed by them in achieving therapeutic efficacy.

Radiation Dose Escalation Is Crucial in Anti-CTLA-4 Antibody Therapy to Enhance Local and Distant Antitumor Effect in Murine Osteosarcoma

“…However, the abscopal effect is rarely observed in treatment of cancers by RT alone, both in preclinical models and in clinical practice. Recently, Honjo et al and Allison et al discovered PD-1 and CTLA-4 antibodies, respectively, which have revolutionized treatments for patients with multiple metastases in various types of cancers, providing a durable long-term response [ 11 , 12 , 13 , 14 , 15 , 16 ]. However, the response is observed for only up to 30% of patients [ 11 , 12 , 13 , 14 , 15 , 16 ].…”

“…Recently, Honjo et al and Allison et al discovered PD-1 and CTLA-4 antibodies, respectively, which have revolutionized treatments for patients with multiple metastases in various types of cancers, providing a durable long-term response [ 11 , 12 , 13 , 14 , 15 , 16 ]. However, the response is observed for only up to 30% of patients [ 11 , 12 , 13 , 14 , 15 , 16 ]. Together with the radiation-induced abscopal effect, combined therapy with immune checkpoint blockade has been found to be an effective strategy for some cancers [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ], although the optimal combination strategy, especially in the context of radiation delivery (e.g., sequence, total dose, and fractionation) remains unclear for some types of tumors.…”

An overview of the tumor microenvironment, from cells to complex networks (Review)

“…An exception is represented by tumors in which there is a strong inflammatory component, where the presence of the Tregs is beneficial (62). They are considered for inhibition through different strategies (60,62) (Table I). B lymphocytes.…”

Resisting Resistance to Immune Checkpoint Therapy: A Systematic Review

“…PD-L1 and CTLA-4 function in peripheral tolerance by activating regulatory T-cells and inhibiting the effector T-cells [ 194 , 195 ]. In mice models, anti-CD134 and anti-CD25 monoclonal antibodies successfully reduced the number of regulatory T-cells within the peripheral lymphoid tissue and caused the regression of tumors [ 196 , 197 ]. Moreover, a complete response was only found in the combination of anti-CD25 and anti-PD-1 [ 196 ].…”

“…On the other hand, the combination of anti-PD-1 with anti-CD134 had a negative effect on the immune system and reduced survival in mouse models [ 198 ]. Studies conducted in rodents showed that targeting folate receptor 4 with monoclonal antibodies led to T reg depletion [ 197 ].…”