Tumor inhibitory T cell immunity may be largely a transplantation artifact not necessarily dependent upon a lack of Treg
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COMMENTARY
Open Access
Tumor inhibitory T cell immunity may be largely a transplantation artifact not necessarily dependent upon a lack of Tregs Richmond T Prehn* and Liisa M Prehn * Correspondence: [email protected] Department of Pathology, University of Washington School of Medicine, Seattle 98118, USA
Abstract There exists a very large literature suggesting that T cells come in a variety of species and that without the action of Tregs tumors would seldom survive inhibition by T cell effectors. We believe that much of the evidence supporting the role of Tregs in cancer is compatible with a perhaps simpler hypothesis based upon the demonstration that that small quantities of effector T cells tend to stimulate tumors while larger quantities of seemingly the same cells are inhibitory (an hormesis-like effect). This possibility seems to destroy much of the need to postulate a role for T cell suppressors (Tregs) in cancer, but the exposure of effector T cells to antigen may convert them into Tregs (Tregs do exist). Furthermore, many other data suggest the possibility that immune inhibition of cancer could be a laboratory artifact seldom if ever seen in unmodified nature.
The Treg hypothesis In the cases of both tumor and normal tissues, Foxp3(+)CD25(+)CD4 regulatory T cells (Tregs) have been thought to be of the essence and are the subject of an extensive literature. Tregs with other antigenic specificities have been described. The basic experiment upon which much of the entire edifice of the Treg cell in cancer appears to have been built is described by North as follows: mice grow tumors because the tumor bearer develops Treg cells that interfere with the T effector cell immune inhibition that might, in the absence of the Tregs, have largely prevented tumor growth [1]. The general Treg thesis is supported by experiments demonstrating that effector T cells often do not inhibit tumor growth in immunodepressed mice when the latter are restored with T cells from both immune and tumor-bearing donors. In contrast, immunodepressed control animals, restored only with normal immune cells, often do not grow that same original tumor [1]. Furthermore, if a tumor is highly immunogenic, it can often be made to regress if the animal is heavily irradiated [2]. This result is supposedly attributable to the unique sensitivity of the Treg cells to ionizing radiation, leaving the T effector population relatively intact. The elimination of Tregs by CTLA-4-blocking antibodies has also demonstrated efficacy in various murine models [3,4]. © 2013 Prehn and Prehn; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Prehn and Prehn Theoretical Biology and Medical Modelling 2013, 10:42 http://www.tbiomed.com/content/10/1/42
The immunostimulation phenomenon It seems there is a logical al
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