Role of the immunosuppressive enzyme indoleamine 2,3-dioxygenase in the progression of ovarian carcinoma

Inaba, Tomoko; Ino, Kazuhiko; Kajiyama, Hiroaki; Yamamoto, Eiko; Shibata, Kiyosumi; Nawa, Akihiro; Nagasaka, Tetsuro; Akimoto, Hidetoshi; Takikawa, Osamu; Kikkawa, Fumitaka

doi:10.1016/j.ygyno.2009.07.015

Cited by 188 publications

(153 citation statements)

References 32 publications

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“…In patients with colorectal cancer, high expression of IDO has been associated with lower CD3 þ Tlymphocyte infiltration in tumor specimens (14). Similarly, CD8 þ T lymphocytes were found in reduced numbers in ovarian cancer tissue in which high IDO expression was detected (15 …”

Section: Tumor-infiltrating Immune Cell Decreasementioning

confidence: 99%

“…In addition, metastases in TDLNs have been found preferentially in patients with endometrial tumors expressing IDO at a high level (26). For patients with this tumor type or for patients with ovarian carcinoma and nasopharyngeal carcinoma, high levels of IDO have been detected in advanced stages of the disease (15,26,27). Polak and colleagues investigated many immunosuppressive molecules in cutaneous melanoma, and IDO expression in positive or negative skin lymph nodes seems to increase with melanoma progression (28).…”

Section: Regulatory T-cell Infiltration Increasementioning

confidence: 99%

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

Godin-Ethier

Hanafi²,

Piccirillo³

et al. 2011

Clinical Cancer Research

344

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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Section: Tumor-infiltrating Immune Cell Decreasementioning

confidence: 99%

Section: Regulatory T-cell Infiltration Increasementioning

confidence: 99%

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

Godin-Ethier

Hanafi²,

Piccirillo³

et al. 2011

Clinical Cancer Research

344

249

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“…CCL22, a protein secreted by dendritic cells and macrophages, highly expressed in tumor ascites is known to have a role in Treg cell migration in tumors 41 . Over-expression of the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) has also been demonstrated in ovarian cancer [44][45][46][47] . IDO suppresses the proliferation of effector T cells or natural killer cells and their killer functions 45,48 .…”

Section: Proteins Involved In Immune Response Modulationmentioning

confidence: 99%

MALDI-MSI and Ovarian Cancer Biomarkers

Longuespée

Boyon²,

Kerdraon³

et al. 2012

Advances in Cancer Management

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“…A tolerogenic activity of IDO, resulting from tryptophan degradation, is to inhibit proliferation and induce apoptosis of effector T-lymphocytes, while simultaneously stimulating FoxP3 þ T reg cell generation (Godin-Ethier et al, 2011). High IDO expression in cancer tissues is associated with lower numbers and impaired function of CD8 þ T-lymphocytes and NK cells (Ino et al, 2008;Liu et al 2009;Wang et al, 2012;Zhang et al, 2011) and, in turn, correlated with a poorer patient prognosis (Inaba et al, 2009;Smith et al, 2012;Yu et al, 2011). A presence of IDO-DC in tumor-draining lymph nodes might contribute to the immunologic unresponsiveness in cancer patients (Godin-Ethier et al, 2011).…”

Section: Ido-dcmentioning

confidence: 99%

Breaking immunotolerance of tumors: A new perspective for dendritic cell therapy

Roliński¹,

Hus

2014

Journal of Immunotoxicology

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The use of dendritic cells (DC) in cancer immunotherapy is based on their potent abilities to present antigens, so they can act as 'natural adjuvants' to enhance immunogenicity of tumor antigens and stimulate specific cytotoxic T-cells. Large amounts of DC can be generated from bone marrow, neonatal cord blood, and peripheral blood CD34 þ hematopoietic stem cells, or from peripheral blood monocytes. The DC can then be pulsed with tumor antigens and reinfused. In vitro, antigen-pulsed DC can stimulate allogeneic T-cell proliferation and induction of autologous specific cytotoxic T-cells; in vivo, the cells inhibit the growth of tumors or protect hosts (i.e. mice) from development of inoculated tumors. The results of preliminary clinical trials have shown that DC vaccines are safe and elicit immune responses; however, the rates of clinical responses are low. It has become quite clear that one key reason for unsatisfactory clinical results is tumor-induced immunosuppression. Among the factors contributing to this type of immunosuppression are populations of regulatory cells including: T-regulatory (T reg ) cells, myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), and DC expressing 2,3-dioxygenase indoleamine (IDO-DC). This review presents an overview of the current understanding about populations of regulatory cells and the most current research efforts directed to overcome immunosuppressive activity due to the tumor microenvironment.

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Role of the immunosuppressive enzyme indoleamine 2,3-dioxygenase in the progression of ovarian carcinoma

Cited by 188 publications

References 32 publications

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

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

MALDI-MSI and Ovarian Cancer Biomarkers

Breaking immunotolerance of tumors: A new perspective for dendritic cell therapy

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