Abstract 1810: The effects of adoptive T cell transfer on the population of regulatory T cells in the mouse colorectal cancer transplant model

Abstract

Abstract Background and Aim: Recent evidence has demonstrated that regulatory T cells (Tregs) mediated immunosuppression is one of the most crutial tumor immune-evasion mechanisms. We clinically demonstrated that the number of peripheral Tregs in the patients with variety of cancer which received ACT, which is non-specific CD3-LAK significantly decreased and that the clinical outcome of the patients of which peripheral Tregs decreased was better. ACT, which contains even only the non-specific lymphocytes might have the potential to not only directly kill malignant cells but also manipulate the population of Tregs in tumor bearing hosts in strong immunosuppressive states. The aim of this study is to investigate the effect of ACT which is composed of non-specific T lymphocytes on the population of Tregs in local tumor, draining lymph nodes and spleen in the mice colorectal cancer transplant model. We have also investigated the effect of activated T cells on the induction of Tregs from CD4+ T cells by IL-2 and TGF-β. Materials and Methods: In vivo study: Male Balb/c mice were injected s.c. with colon26. The population of Treg in the tumor, the lymph node, and the spleen was analyzed after ACT(non-specific CD3-LAK) administration via a tail vein. In vitro study: The inducible system of Tregs was established. CD4+cells sorted from murine splenocytes were expanded for 72 hours in culture media containing IL-2 and TGFβ. LAK cells were co-cultured non-contactly with CD4+cells. Then we investigated the changes in the system after the co-culture. We also measured the concentration of IFN-γ in the culture solution to reveal the mechanism. Results: The accumulation of Tregs in the draining LNs and tumor was significantly suppressed by ACT. The induction of Tregs in vitro was inhibited by co-culture with LAK cells. The concentration of IFN-γ in the culture solution increased in LAK+ group.Conclusions: We have demonstrated that ACT has the potential to reduce the number of Tregs in tumor and draining lymph nodes in the mouse colorectal cancer transplant model. As one of the mechanisms of this phenomenon, IFN-γ secreted from LAK cells might blockade the conversion of CD4+ cells into Tregs. These findings suggest a novel therapeutic position of ACT in variety of cancer immunotherapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1810. doi:10.1158/1538-7445.AM2011-1810