Regulatory T cells, tumour immunity and immunotherapy

An active process of tolerization takes place in the tumour microenvironment. Induction of trafficking, differentiation and expansion of regulatory T cells is a crucial tumour immune-tolerizing mechanism and is also one of the main obstacles tempering successful immunotherapy.Interactions between cancer cells and host immune cells in the tumour microenvironment create an immunosuppressive network. Regulatory T cells are substantially recruited to the tumour through tumour environmental chemokine(s).Tumour environmental regulatory T cells might use multiple suppressive mechanisms to reduce tumour-associated antigen (TAA)-specific T-cell immunity. A novel suppressive mechanism is that regulatory T cells convey suppressive capacity to antigen-presenting cells (APCs) through induction of B7-H4 expression.CD4+CD25+ regulatory T cells (TReg cells) accumulate in the tumour environment and reduce TAA-specific immunity, and their presence can be used to predict patient survival. Data from clinical trials of depletion of regulatory T cells are immunologically and therapeutically interesting.Current immunotherapeutic and vaccine regimens including interleukin-2 (IL-2) administration and APC vaccination could potentially promote regulatory T-cell function in vivo and need careful re-evaluation with regard to beneficial versus detrimental effects. IL-2 could be therapeutically replaced by other common cytokine-receptor γ-chain cytokines.Depletion of regulatory T cells or reduction of regulatory T-cell suppressive activity are two promising strategies that could either work alone or in combination to improve current tumour therapies. It is time to consider combinational immunotherapy, including reverting suppressive mechanisms, supplementing active immune elements and suppressing tumour growth and angiogenesis.