Naturally occurring CD25(+)CD4(+) regulatory Tcells (T-R cells), which specifically express the transcription factor Foxp3, engage in the maintenance of immunological self-tolerance and Suppressive control of aberrant or excessive immune responses to foreign antigens. They may, oil the other hand, impede immune surveillance against cancer and hamper the development of effective immunity to autologous tumor cells. Indeed, natural TR cells have been observed to predominantly infiltrate tumor masses especially in the early phase Of tumor progression. Depletion of natural TR cells by removing CD25(+) T cells prior to tumor challenge is therefore able to provoke effective tumor immunity in animals. Futhermore, attenuation of T-R cell-mediated suppression in on-going anti-tumor immune responses, for example by altering signaling through CTLA-4 Or GITR expressed by natural TR cells, call enhance the responses and thereby eradicate advanced cancers. A combination of depletion or attenuation of T-R cells and concomitant stimulation of effector T cells, systemically or locally in tumors, may be a feasible immunotherapy for cancer. (c) 2005 Elsevier Ltd. All rights reserved.
