T-regulatory cells immunotherapy

T-regulatory cell (Treg) targeting in immunotherapy

T-regulatory cells (Treg) and Immunotherapy

T-regulatory cells (Treg), suppress an aberrant immune response against self-antigens, and they also suppress anti-tumor immune responses. Infiltration of a large number of Treg cells into tumor tissues is often associated with poor prognosis. There is accumulating evidence that the removal of Treg cells is able to evoke and enhance anti-tumor immune response. However, systemic depletion of Treg cells may concurrently elicit deleterious autoimmunity.

One strategy used at the Integrative Cancer Treatment & Research Center (ICT-RC) for evoking effective tumor immunity without autoimmunity is to specifically target terminally differentiated effector T-regulatory cells because effector Treg cells are the predominant cell type in tumor tissues. Various cell surface molecules, including chemokine receptors such as CCR4, that are specifically expressed by effector T-regulatory cells can be the candidates for depleting effector T-regulatory cells by specific cell-depleting monoclonal antibodies.

In addition, other immunological characteristics of effector T-regulatory cells, such as their high expression of CTLA-4, active proliferation, and apoptosis-prone tendency, can be exploited to control specifically their functions.

For example, anti-CTLA-4 antibody may kill effector Treg cells or attenuate their suppressive activity. By either having either a tumor biopsy and/or  tumor tissue analysis, the Treg cells and antigens associated within the tumor itself can be targeted. A combination of T-regulatory cell targeting (e.g., by reducing Treg cells or attenuating their suppressive activity in tumor tissues) with the activation of tumor-specific effector T cells (e.g., by cancer vaccine (dendritic cell) or immune checkpoint blockade) current cancer immunotherapy can be more effective.

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