2016
DOI: 10.18632/oncotarget.8488
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Lung cancer-derived galectin-1 contributes to cancer associated fibroblast-mediated cancer progression and immune suppression through TDO2/kynurenine axis

Abstract: Communication between cancer cells and their microenvironment plays an important role in cancer development, but the precise mechanisms by which cancer-associated fibroblasts (CAF) impact anti-cancer immunity and cancer progression in lung cancer are poorly understood. Here, we report that lung fibroblasts when activated by lung cancer cells produce tryptophan metabolite kynurenine (Kyn) that inhibits dendritic cells' differentiation and induces cancer growth as well as migration. We identified TDO2 (tryptopha… Show more

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Cited by 116 publications
(101 citation statements)
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References 38 publications
(47 reference statements)
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“…In the present study, we showed that Ido2 deletion enhanced CD8 + cell invasion in the tumor microenvironment, and inhibited tumor growth in an LLC mouse model. This resulted from increases in tryptophan and decreases in kynurenine levels in the tumor microenvironment, which confirmed the results of previous reports, although the enzyme activity of Ido2 is much lower than that of Ido1. From these results the change in tryptophan metabolism caused by not only Ido1 and Tdo2, but also Ido2, was important in the induction of immune tolerance in tumors.…”
Section: Discussionsupporting
confidence: 91%
See 1 more Smart Citation
“…In the present study, we showed that Ido2 deletion enhanced CD8 + cell invasion in the tumor microenvironment, and inhibited tumor growth in an LLC mouse model. This resulted from increases in tryptophan and decreases in kynurenine levels in the tumor microenvironment, which confirmed the results of previous reports, although the enzyme activity of Ido2 is much lower than that of Ido1. From these results the change in tryptophan metabolism caused by not only Ido1 and Tdo2, but also Ido2, was important in the induction of immune tolerance in tumors.…”
Section: Discussionsupporting
confidence: 91%
“…29 In addition, the treatment with a Tdo2 inhibitor improves dendritic cell function and T cell response significantly, leading to decreased tumor metastasis in mice. 30 F I G U R E 3 Levels of infiltrating immune cells at tumor sites in WT and indoleamine 2,…”
Section: Discussionmentioning
confidence: 99%
“…For example, tumor cells manipulate surrounding adipocytes to increase lipolysis to whet their appetite for fatty acids (Nieman et al, 2011). Cancer associated fibroblasts degrade tryptophan that not only starves immune cells in the local environment of an essential amino acid, but also leads to the production of the immunosuppressive metabolite kynurenine (Hsu et al, 2016). Moreover, glucose is a critical substrate for the antitumor functions of effector T cells and M1 macrophages, which both require engagement of aerobic glycolysis for their activation and full effector functions (Buck et al, 2015; O’Neill and Pearce, 2016).…”
Section: The Tumor Microenvironmentmentioning
confidence: 99%
“…Cancer‐associated fibroblasts can also promote the invasion and metastasis of tumour cells. Cancer‐associated fibroblasts produce the tryptophan metabolite kynurenine and were shown to inhibit the differentiation of DCs and promote tumour cell growth and migration in lung cancer . Galectin‐1 upregulated tryptophan 2,3‐dioxygenase (TDO2) expression in CAFs.…”
Section: Regulation Of Cancer‐associated Fibroblasts In Cancermentioning
confidence: 99%
“…Cancer-associated fibroblasts produce the tryptophan metabolite kynurenine and were shown to inhibit the differentiation of DCs and promote tumour cell growth and migration in lung cancer. 9 Galectin-1 upregulated tryptophan 2,3-dioxygenase (TDO2) expression in CAFs. The inhibition of TDO2 decreased tumour metastasis by promoting the T cell response in vivo.…”
Section: Reg Ul Ati On Of C An Cer-a Sso Ciated Fib Rob L a S Ts Inmentioning
confidence: 99%