Decrease of the Regulatory T-Cell Population by Adoptive T-Cell Transfer in a Mouse Colorectal Cancer Transplant Model

Authors: Matsumoto, Tsuguhiro; Kokura, Satoshi; Ishikawa, Takeshi; Funaki, Jun; Adachi, Satoko; Mori, Koji; Sakamoto, Naoyuki; Katada, Kazuhiro; Kamada, Kazuhiro; Yagi, Nobuaki; Handa, Osamu; Takagi, Tomohisa; Uchiyama, Kazuhiko; Naito, Yuji; Yosikawa, Toshikazu

Source: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 1 December 2012, vol. 19, no. 12, pp. 543-554(12)

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Abstract:

We examined the effects of adoptive T-cell transfer (ACT) on the population of regulatory T cells (Tregs) in a mouse colorectal cancer transplant model. In an in vivo study, Treg populations in Balb/c mice colon26 transplant model after ACT were analyzed in peripheral blood, local lymph node, and tumor. In an in vitro study CD4+ cells were cultured in medium containing TGF-β to induce Tregs. LAK cells were added or not in this Treg induction system. Treg induction after coculture with LAK was investigated. We also studied the role of IFN-γ in the mechanism of Treg induction. Tregs in the draining lymph nodes and tumor were significantly suppressed by ACT. The induction of Tregs in vitro was inhibited by coculture with LAK cells. Furthermore, Tregs in the cultured cells were significantly inhibited by addition of exogenous IFN-γ. Moreover, Tregs were increased by addition of IFN-γ mAb. ACT may decrease Tregs in tumor-bearing hosts. One of the mechanisms is considered to be IFN-γ inhibiting the induction of Tregs.

Keywords: Adoptive T-cell transfer (ACT); Cancer; Interferon-γ (INF-γ); Regulatory T cells (Tregs)

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096504012X13340632812596

Publication date: December 1, 2012

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