HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Leon, K. Articles by Lage, A. Search for Related Content PubMed PubMed Citation Articles by Leon, K. Articles by Lage, A.

How Regulatory CD25⁺CD4⁺ T Cells Impinge on Tumor Immunobiology: The Differential Response of Tumors to Therapies

Kalet Leon^1,*,, Karina Garcia^*, Jorge Carneiro and Agustin Lage^*

^* Centro de Inmunología Molecular, Havana, Cuba; and Instituto Gulbenkian de Ciência, Oeiras, Portugal

Aiming to get a better insight on the impact of regulatory CD25⁺CD4⁺ T cells in tumor-immunobiology, a simple mathematical model was previously formulated and studied. This model predicts the existence of two alternative modes of uncontrolled tumor growth, which differ on their coupling with the immune system, providing a plausible explanation to the observation that the development of some tumors expand regulatory T cells whereas others do not. We report now the study of how these two tumor classes respond to different therapies, namely vaccination, immune suppression, surgery, and their different combinations. We show 1) how the timing and the dose applied in each particular treatment determine whether the tumor will be rejected, with or without concomitant autoimmunity, or whether it will continue progressing with slower or faster pace; 2) that both regulatory T cell-dependent and independent tumors are equally sensitive to vaccination, although the former are more sensitive to T cell depletion treatments and are unresponsive to partial surgery alone; 3) that surgery, suppression, and vaccination treatments, can synergistically improve their individual effects, when properly combined. Particularly, we predict rational combinations helping to overcome the limitation of these individual treatments on the late stage of tumor development.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Kalet Leon, Instituto Gulbenkian de Ciencia, Rua da Quinta Grande, no 6, Apartado 14, Oeiras, Portugal. E-mail address: kalet{at}cim.sld.cu and kalet1{at}yahoo.com

² Abbreviations used in this paper: T_R cells, regulatory T cells; T_E, effector T cells; LN, lymph node.