T-regulatory cells in tumour-specific vaccination strategies

Abstract

Background: Immunotherapy against cancer does not result in impressive clinical responses. Failure of vaccine-induced T-cell-mediated immunotherapy to improve therapeutic results occurs for many reasons, including regulatory networks imposed by growing tumours, intrinsic properties of cancer cells, suboptimal design of therapeutic vaccines and subversion of the immune system. Most vaccines are incapable of inducing strong immunity, the vaccine's capacity to induce effector T cells is blocked by regulatory T cells (Tregs) in the lymph nodes, the vaccine-induced T cells are not able to infiltrate the tumour, tumour-infiltrating T cells cannot exert their effector function due to locally present Tregs and/or vaccines may induce/boost Tregs. Objective/methods: We focus on the negative effects of Tregs in cancer immunotherapy and highlight potential therapeutic options to counteract these. Conclusions: Interplay and balance between Tregs and effector cells determines the efficacy of vaccines and thereby clinical outcome.

Keywords::

• cancer
• immunotherapy
• regulatory T cells
• vaccine

Acknowledgments

The authors apologise to those involved with all the excellent research that could not be cited because of space limitations. This study was supported by grants from NWO Zon/Mw 917.56.311 and by the Dutch Cancer Society 2007-33848 to SHvdB.