The Impact of Indoleamine 2,3-dioxygenase (IDO) Expression on Stage III Gastric Cancer

Nishi, Masaaki; Yoshikawa, Kozo; Higashijima, Jun; Tokunaga, Takuya; Kashihara, Hideya; Takasu, Chie; Ishikawa, Daichi; Wada, Yuma; Shimada, Mitsuo

doi:10.21873/anticanres.12605

Cited by 26 publications

(22 citation statements)

References 23 publications

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“…It has two isoforms, IDO1 and IDO2, whose genes are adjacent and have distinct biochemical features supporting their functions 18, 19. IDO1 plays an immune-regulatory role 20. It is a cytosolic enzyme distributed in various organs, such as the lung, spleen, liver, kidney and brain.…”

Section: Enzymes Involved In the Kyn Pathway: Ido And Tdomentioning

confidence: 99%

Role of IDO and TDO in Cancers and Related Diseases and the Therapeutic Implications

Ye¹,

Yue²,

Shi³

et al. 2019

J. Cancer

143

112

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Kynurenine (Kyn) pathway is a significant metabolic pathway of tryptophan (Trp). The metabolites of the Kyn pathway are closely correlated with numerous diseases. Two main enzymes, indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO or TDO2), regulate the first and rate-limiting step of the Kyn pathway. These enzymes are directly or indirectly involved in various diseases, including inflammatory diseases, cancer, diabetes, and mental disorders. Presently, an increasing number of potential mechanisms have been revealed. In the present review, we depict the structure of IDO and TDO and explicate their functions in various diseases to facilitate a better understanding of them and to indicate new therapeutic plans to target them. Moreover, we summarize the inhibitors of IDO/TDO that are currently under development and their efficacy in the treatment of cancer and other diseases.

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Section: Enzymes Involved In the Kyn Pathway: Ido And Tdomentioning

confidence: 99%

Role of IDO and TDO in Cancers and Related Diseases and the Therapeutic Implications

Ye¹,

Yue²,

Shi³

et al. 2019

J. Cancer

143

112

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“…IDO1 plays an importnat role in suppression of CTLs in gastric cancer and, accordingly, it was recently proposed as a new, negative prognostic biomarker for overall survival of gastric cancer patients. 78–82 Cytotoxicity and capacity for proliferation of CTLs, obtained from gastric cancer patients, were significantly attenuated when these cells were cocultured with IDO1 overexpressing human gastric cancer BGC-823 cells. 78 An addition of 1-methyl-tryptophan, a competitive inhibitor of IDO1, to the CTLs (BGC-823 culture) completely restored antitumor properties of CTLs, confirming the importance of IDO1 for suppression of CTLs.…”

Section: The Role Of Ido1 In the Development And Progression Of Gastrmentioning

confidence: 99%

Role of indoleamine 2,3-dioxygenase in pathology of the gastrointestinal tract

Acović

Gazdic

Jovičić

et al. 2018

Therap Adv Gastroenterol

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Indoleamine 2,3-dioxygenase (IDO) has the most important role in modulation of tryptophan-dependent effects in the gastrointestinal tract, including modulation of intestinal immune response. An increased IDO activity maintains immune tolerance and attenuates ongoing inflammation but allows immune escape and uncontrolled growth of gastrointestinal tumors. Accordingly, IDO represents a novel therapeutic target for the treatment of inflammatory and malignant diseases of the gastrointestinal tract. In this review article, we summarize current knowledge about molecular and cellular mechanisms that are involved in IDO-dependent effects. We provide a brief outline of experimental and clinical studies that increased our understanding of how enhanced IDO activity: controls host–microbiota interactions in the gut; regulates detrimental immune response in inflammatory disorders of the gastrointestinal system; and allows immune escape and uncontrolled growth of gastrointestinal tumors. Additionally, we present future perspectives regarding modulation of IDO activity in the gut as possible new therapeutic approaches for the treatment of inflammatory and malignant diseases of the gastrointestinal system.

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“…CMTM6 controls PD-L1 expression (3,4). We previously reported PD-1 expression in gastric cancer patients and that PD-L1 expression or Indoleamine 2,3-dioxygenase (IDO) correlated with a poor prognosis in gastric cancer after curative resection (1,15). Furthermore, PD-1 expression was correlated with PD-L1 expression (1).…”

Section: Discussionmentioning

confidence: 99%

Impact of CKLF-like MARVEL Transmembrane Domain Containing 6 (CMTM6) Expression in Gastric Cancer

Nishi

Shimada

Yoshikawa

et al. 2020

Preprint

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Background: CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is the master regulator of programmed cell death-ligand 1(PD-L1). We aimed to clarify the significance of CMTM6 expression in gastric cancer (GC). Methods: A total of 105 patients who had undergone curative surgical resection for stage II/III GC at Tokushima University Hospital were included in this study. The expression of CMTM and PD-L1 was examined by immunohistochemistry. Additionally, the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. Results: CMTM6 was not positively correlated with any of the factors examined. The overall survival (OS) rates were significantly poorer in the CMTM6 high-expression group than in the CMTM low-expression group (5-year OS: 57.2% vs. 79.2%, respectively; p<0.05). Disease-free survival (DFS) was significantly poorer in the CMTM high-expression group than in the CMTM6 low-expression group (5-year DFS: 52.8% vs. 72.4%, respectively; p=0.20). Multivariate analysis confirmed CMTM6 expression as an independent prognostic factor in DFS (p<0.05). CMTM6 expression tended to be correlated with PD-L1 expression (p=0.07), and PD-L1 expression was positively correlated with PD-1 expression (p<0.05).Conclusions: CMTM6 is associated with a poor prognosis and immunotolerance through PD-L1 in GC.

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The Impact of Indoleamine 2,3-dioxygenase (IDO) Expression on Stage III Gastric Cancer

Abstract: IDO is associated with poor prognosis and immuno-tolerance through attenuation of Treg activation in Stage III GC.

Cited by 26 publications

References 23 publications

Role of IDO and TDO in Cancers and Related Diseases and the Therapeutic Implications

Role of IDO and TDO in Cancers and Related Diseases and the Therapeutic Implications

Role of indoleamine 2,3-dioxygenase in pathology of the gastrointestinal tract

Impact of CKLF-like MARVEL Transmembrane Domain Containing 6 (CMTM6) Expression in Gastric Cancer

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