Indoleamine 2,3-dioxygenase (IDO): Only an enzyme or a checkpoint controller?

Bilir, Cemil; Sarısözen, Can

doi:10.1016/j.jons.2017.04.001

Cited by 91 publications

(70 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Tremelimumab, a humanized anti‐CTLA‐4 monoclonal antibody, was prescribed to refractory CRC patients with better tolerability (Ribas, 2010). IDO is an intracellular enzyme that establishes immunosuppressive effects and escape of tumor cells from immune responses by causing tryptophan depletion (Bilir & Sarisozen, 2017). The GDC‐0919 and epacadostat molecules are among the anti‐IDO agents in clinical trials.…”

Section: Immunotherapy Of Colorectal Cancer By Focusing On Pd‐1/pd‐l1mentioning

confidence: 99%

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

Payandeh

Khalili

Somi

et al. 2020

Journal Cellular Physiology

View full text Add to dashboard Cite

Colorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death‐1 (PD‐1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD‐1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD‐ligand 1 (PD‐L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD‐L1 by conventional chemotherapeutics, we have summarized the role of PD‐L1 in CRC, the chemotherapy effects on the PD‐1/PD‐L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD‐L1.

show abstract

Section: Immunotherapy Of Colorectal Cancer By Focusing On Pd‐1/pd‐l1mentioning

confidence: 99%

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

Payandeh

Khalili

Somi

et al. 2020

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Some of the immunosuppressive mechanisms found in viral and bacterial infections, as well as in tumors, are the metabolic changes that come from the overexpression of the enzyme indoleamine 2,3‐dioxygenase (IDO) . IDO is an immunoregulatory enzyme that catalyzes the rate‐limiting step of tryptophan (Trp) metabolism through the kynurenine (Kyn) pathway.…”

Section: Introductionmentioning

confidence: 99%

Indoleamine 2,3‐dioxygenase and tryptophan 2,3‐dioxygenase expression in HPV infection, SILs, and cervical cancer

Venancio

Consolaro

Derchain

et al. 2019

Cancer Cytopathology

View full text Add to dashboard Cite

BACKGROUND: Human papillomavirus (HPV) infection is the central factor for cervical cancer, whereas epithelial immune mechanisms contribute to the progression of HPV infection and its associated lesions. The authors evaluated the expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) in cervicovaginal samples from women with normal cervical epithelium or with different degrees of squamous intraepithelial lesions (SILs) and cervical cancer. METHODS: IDO expression was analyzed by immunocytochemistry in liquid-based cytology samples from 165 women, of whom 42 had cervical changes subclassified as low-grade SIL (n = 6), high-grade SIL (n = 30), or squamous cell carcinoma (SCC) (n = 6), and 123 had negative Papanicolaou smears. IDO and TDO expression also were analyzed by immunohistochemistry, and HPV and other genital pathogens were evaluated by polymerase chain reaction analysis. RESULTS: Low IDO expression was observed in normal cervical epithelium irrespective of HPV status. Increased numbers of IDO-positive squamous cells and IDO-positive leukocytes were observed in women with SIL or SCC. TDO expression was detected in leukocytes infiltrating the stroma around intraepithelial or invasive cervical lesions. Higher IDO levels were detected in organotypic epithelial cultures established from keratinocytes transduced with the HPV16 E6/E7 oncoproteins. CONCLUSIONS: The upregulation of IDO expression in leukocytes and squamous cells in HPVassociated SIL and SCC suggests that immunosuppressive mechanisms involving tryptophan metabolism may have a role in cervical carcinogenesis. Although previous studies have suggested the role of IDO in HPV pathogenesis, this is the first evidence of TDO involvement in the process. Furthermore, the current data emphasize the role of leukocytes, especially neutrophil-like cells, as an IDO source.We gratefully acknowledge the collaboration of Luiz Carlos Zeferino, Júlio Cesar Teixeira, and Luiz Bahamondes for their assistance to the women included in this study and Maria Cecília Costa and Fabrícia Gimenez for their assistance with polymerase chain reaction analyses.Additional supporting information may be found in the online version of this article.

show abstract

“…Suppression of monocyte function can also occur by the IFN-induced tryptophan-catabolizing enzyme indoleamine 2,3dioxygenase (IDO) (Musso et al, 1994). Activated IDO depletes tryptophan levels and this depletion induces cell cycle arrest of T cells, ultimately increasing their apoptosis and causing immunosuppressive effects (Bilir and Sarisozen, 2017). It has been shown that IL-4 can inhibit IDO expression (Musso et al, 1994), so in the absence of responsiveness to IL-4, it is possible that DCs of CD11c cre IL-4R α−/lox mice would have increased IDO expression, resulting in a more suppressive phenotype.…”

Section: Discussionmentioning

confidence: 99%