Forkhead box P3 regulatory T cells coexisting with cancer associated fibroblasts are correlated with a poor outcome in lung adenocarcinoma. Issue 4 (19th February 2013)

• Record Type: Journal Article
• Authors: Kinoshita, Tomonari; Ishii, Genichiro; Hiraoka, Nobuyoshi; Hirayama, Shunki; Yamauchi, Chisako; Aokage, Keiju; Hishida, Tomoyuki; Yoshida, Junji; Nagai, Kanji; Ochiai, Atsushi
• Is Part Of: Cancer science. Volume 104:Issue 4(2013:Apr.)
• Page Start: 409
• Page End: 415
• Publication Date: 2013-02-19
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.12099
• Languages: English
• ISSNs: 1347-9032

Abstract

<abstract abstract-type="main" id="cas12099-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Recently, an association between tumor infiltrating Forkhead box P3 regulatory T cells (T<sub>reg</sub>) and an unfavorable prognosis has been clinically shown in some cancers, but the mechanism of T<sub>reg</sub> induction in the tumor microenvironment remains uncertain. The aims of the present study were to examine the relationship between T<sub>reg</sub> and patient outcome and to investigate whether T<sub>reg</sub> induction is influenced by the characteristics of cancer‐associated fibroblasts (CAF) in lung adenocarcinoma. The numbers of T<sub>reg</sub> in both the tumor stroma and the tumor nest were counted in 200 consecutive pathological stage I lung invasive adenocarcinoma specimens. To examine whether the characteristics of CAF influence T<sub>reg</sub> induction, we selected and cultured CAF from low T<sub>reg</sub> and high T<sub>reg</sub> adenocarcinoma. The number of T<sub>reg</sub> was much higher in the stroma than in the nest (<italic>P </italic><<italic> </italic>0.01). Patients with high T<sub>reg</sub> had a significantly poorer prognosis than those with low T<sub>reg</sub> (overall survival: <italic>P </italic>=<italic> </italic>0.03; recurrence‐free survival: <italic>P </italic>=<italic> </italic>0.02; 5‐year overall survival: 85.4% <italic>vs</italic> 93.0%). Compared with the CAF from low T<sub>reg</sub> adenocarcinoma, culture supernatant of the CAF from high T<sub>reg</sub> adenocarcinoma induced more T<sub>reg</sub> (<italic>P </italic>=<italic> </italic>0.01). Also, CAF from high T<sub>reg</sub> adenocarcinoma expressed significantly higher mRNA levels of transforming growth factor‐β (<italic>P </italic>=<italic> </italic>0.01) and vascular endothelial growth factor (<italic>P </italic>=<italic> </italic>0.01), both of which are involved in T<sub>reg</sub> induction. Our studies suggest the possibility that CAF expressing immunoregulatory cytokines may induce T<sub>reg</sub> in the stroma, creating a tumor‐promoting microenvironment in lung adenocarcinoma that leads to a poor outcome.</p> </abstract>