Expression and prognosis role of indoleamine 2,3-dioxygenase in hepatocellular carcinoma

Pan, Ke; Wang, Hui; Chen, Min Shan; Zhang, Hua Kun; Weng, De Sheng; Zhou, Jun; Huang, Wei; Li, Jian Jun; Song, Hai; Xia, Jian Chuan

doi:10.1007/s00432-008-0395-1

Cited by 154 publications

(128 citation statements)

References 30 publications

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“…immune cells in the tumor microenvironment were also evaluated. Detection of immunosuppressive markers including PD-L1, CTLA-4, and IDO has been reported for various tumor types [4,[15][16][17][18][19][20][21][22][23][24][25][26][27]. In our study, the positive expression of PD-L1, CTLA-4, and IDO was noted in 43.6, 65.8, and 47.7 % of the cases, respectively.…”

Section: Discussionsupporting

confidence: 59%

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer

et al. 2014

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Background There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric cancer (GC). Methods In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression [programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO)] in tumors and the densities of immune cells [CD3(?), CD4(?), CD8(?), or PD-1(?) cells] within the tumor microenvironment were measured using immunohistochemical analysis. Results Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7 % of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/ moderately differentiated adenocarcinoma (P \ 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC [PD-L1(?) vs. PD-L1(-) tumors: 5-year DFS rate, 82.6 vs. 66.9 %; 5-year OS rate, 83.0 vs. 69.1 % (P values \0.05)]. Survival outcomes were also better in patients with a higher density of CD3(?) cells within the tumor microenvironment than in those with a lower density of CD3(?) cells [5-year DFS rate, 80.9 vs. 67.0 %; 5-year OS rate, 82.5 vs. 68.0 % (P values \0.05)]. In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables. Conclusions GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(?) expression and a high-CD3 tumor microenvironment are favorable prognostic markers in GC.

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Section: Discussionsupporting

confidence: 59%

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer

et al. 2014

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“…On the one hand, frequency of hepatic metastasis has been found to be significantly increased in patients with colorectal cancer presenting high IDO expression in their tumor (14). Strong IDO expression in hepatocellular tumors has also been associated with the presence of distant metastases (25). In addition, metastases in TDLNs have been found preferentially in patients with endometrial tumors expressing IDO at a high level (26).…”

Section: Regulatory T-cell Infiltration Increasementioning

confidence: 99%

“…In 2 studies, IDO expression evaluated by immunohistochemistry (IHC) and enzymatic activity has been inversely correlated with progression-free survival (16,26,31). Also, IDO measurement by IHC in hepatocellular carcinoma samples from 138 patients has established that low IDO expression correlates with an improved overall survival (25). For patients with invasive cervical cancer treated with radical hysterectomy, it has been observed that focal and diffuse IDO expression in cancer tissue correlates with decreased overall and progression-free survival, whereas patients with no IDO expression in their tumor had a better survival (30).…”

Section: Association With Patient Survivalmentioning

confidence: 99%

Indoleamine 2,3-Dioxygenase Expression in Human Cancers: Clinical and Immunologic Perspectives

Godin-Ethier

Hanafi²,

Piccirillo³

et al. 2011

Clinical Cancer Research

348

249

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Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme with immune-regulating activities in many contexts, such as fetal protection, allograft protection, and cancer progression. Clinical trials are currently evaluating IDO inhibition with 1-methyltryptophan in cancer immunotherapy. However, the exact role of tryptophan catabolism by IDO in human cancers remains poorly understood. Here, we review several studies that correlate IDO expression in human cancer samples and tumor-draining lymph nodes, with relevant clinical or immunologic parameters. IDO expression in various histologic cancer types seems to decrease tumor infiltration of immune cells and to increase the proportion of regulatory T lymphocytes in the infiltrate. The impact of IDO on different immune cell infiltration leads to the conclusion that IDO negatively regulates the recruitment of antitumor immune cells. In addition, increased IDO expression correlates with diverse tumor progression parameters and shorter patient survival. In summary, in the vast majority of the reported studies, IDO expression is correlated with a less favorable prognosis. As we may see results from the first clinical trials with 1-methyltryptophan in years to come, this review brings together IDO studies from human studies and aims to help appreciate outcomes from current and future trials. Consequently, IDO inhibition seems a promising approach for cancer immunotherapy.

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“…As in DCs, monocytes, and macrophages, an inverse correlation has been found in many tumour types between IDO expression and the number of tumour infiltrating CD8+ T cells (Brandacher et al 2006, Inaba et al 2009, Ino et al 2008, and Uyttenhove et al 2003. Overexpression of IDO by malignant cells is an important cancer induced immune escape mechanism and has been associated with poor prognoses for survival (Brandacher et al 2006, Inaba et al 2009, Ino et al 2008, Risenberg et al 2007, Inaba et al 2010, and Pan et al 2008. This finding, however, has increased the potential of using IDO inhibitors, such as 1-MT, in cancer treatments.…”

Section: Ido and Immunosuppressionmentioning

confidence: 98%

Immuno-modulatory Role of Indoleamine 2, 3-Dioxygenase in Allogeneic Islet and Skin Transplantation

Gill¹,

Jalili²,

Ghahary³

2013

IMMU

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Indoleamine 2, 3-dioxygenase (IDO) is a naturally occurring immunomodulatory agent that has been found to play a key role in preventing rejection of the semi-allogeneic fetus during pregnancy. It is a cytosolic monomeric hemoprotein enzyme that degrades tryptophan, the least available essential amino acid in the body, through the kynurenine metabolic pathway. This causes a regulatory effect on T cells by, as it has been proposed, causing toxic tryptophan metabolites to accumulate and a tryptophan deficient microenvironment to form. By helping with the induction of T cell unresponsiveness, IDO has been shown to establish immune tolerance and control autoreactive immune responses. Thus, the application of IDO's ability to do this may have a huge potential in improving the rates of acceptance of insulin producing islet cell or skin graft transplants in patients suffering from conditions such as type I diabetes or burn injuries, respectively. The discovery of an agent able to do this is especially important since currently used systemic immunosuppressive drugs carry many side effects and cause complications that make the long term use of these agents problematic after transplantation. This review discusses the immunomodulatory role of IDO and the very promising results of studies done by our research group on the application of this enzyme in islet and skin transplantation.

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Expression and prognosis role of indoleamine 2,3-dioxygenase in hepatocellular carcinoma

Abstract: Our data indicated that IDO may be a novel favorable prognostic indicator and candidate adjuvant therapeutic target for HCC.

Cited by 154 publications

References 30 publications

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer

Indoleamine 2,3-Dioxygenase Expression in Human Cancers: Clinical and Immunologic Perspectives

Immuno-modulatory Role of Indoleamine 2, 3-Dioxygenase in Allogeneic Islet and Skin Transplantation

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