Regulatory-T-cell inhibition versus depletion: the right choice in cancer immunotherapy.
Tumour-induced expansion of regulatory T (T(Reg)) cells is an obstacle to successful cancer immunotherapy. The potential benefit of T(Reg)-cell depletion through the interleukin-2 receptor is lost by the concurrent elimination of activated effector lymphocytes and possibly by the de novo induction of T(Reg)-cell replenishment. In theory, the functional inactivation of T(Reg) cells will maintain them at high numbers in tumours and avoid their replenishment from the peripheral lymphocyte pool, which has the capacity to further suppress the effector lymphocyte anti-tumour response.
Colombo
Mario P
MP
Fondazione IRCCS Istituto Nazionale Tumori Experimental Oncology, Via G. Venezian 1, Milan, 20133 Italy. mario.colombo@istitutotumori.mi.it
Piconese
Silvia
S
D000241:Adenosine / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors; D053645:Interleukin-2 Receptor alpha Subunit / Q000187:drug effects / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D053262:Receptors, OX40 / Q000819:agonists / Q000276:immunology; D017634:Self Tolerance; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053645:Interleukin-2 Receptor alpha Subunit; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; D000241:Adenosine