Neutrophils are Essential in Short Hairpin RNA of Indoleamine 2,3- Dioxygenase Mediated-antitumor Efficiency

Liu, Kuan‐Ting; Liu, Yaohua; Liu, Hsin-Liang; Chong, Inn‐Wen; Yen, Meng‐Chi; Kuo, Po‐Lin

doi:10.1038/mtna.2016.105

Cited by 7 publications

(20 citation statements)

References 46 publications

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“…Previous reports have indicated that Ido1‐knockout mice have reduced tumor growth in an LLC model . Furthermore, the Ido1 inhibitor, 1 methyl tryptophan (1‐MT), inhibits tumor growth in vivo . In addition, the treatment with a Tdo2 inhibitor improves dendritic cell function and T cell response significantly, leading to decreased tumor metastasis in mice …”

Section: Discussionmentioning

confidence: 99%

“…28 Furthermore, the Ido1 inhibitor, 1 methyl tryptophan (1-MT), inhibits tumor growth in vivo. 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%

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Indoleamine 2,3‐dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma

et al. 2019

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Tryptophan metabolism is important to induce immune tolerance in tumors. To date, 3 types of tryptophan‐metabolizing enzymes have been identified: indoleamine 2,3‐dioxygenase 1 and 2 (IDO1 and IDO2) and tryptophan 2,3‐dioxygenase 2. Numerous studies have focused on IDO1 as its expression is enhanced in various cancers. Recently, IDO2 has been identified as a tryptophan‐metabolizing enzyme that is involved in several immune functions and expressed in cancers such as pancreatic cancer. However, the biological role of IDO2 in the induction of immune tolerance in tumors has not yet been reported. In the present study, we examined the effects of Ido2 depletion on tumor growth in a mouse model of Lewis lung carcinoma by using Ido2‐knockout mice. Ido2‐knockout mice had reduced tumor volumes compared to WT mice. Furthermore, Ido2 depletion altered the tumor microenvironment, such as tryptophan accumulation and kynurenine reduction, leading to enhancement of immune cell invasion. Finally, enzyme‐linked immunospot assay revealed that Ido2 depletion enhanced γ‐interferon secretion in the tumor. In conclusion, Ido2 is an important immune regulator in the tumor microenvironment. Our data indicate that IDO2 is a potential target for cancer treatment and drug development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3‐dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma

et al. 2019

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“…54 Munn et al observed that IDO overactivation could lead to an increase in the level of uncharged tRNA Trp . 56 In addition, host tRNAs are involved in various processes such as viral translation and reverse transcription, performing vital functions in regulating viral virulence and immunogenicity. 55 In the LLC1 lung cancer model, short hairpin against IDO (IDO shRNA) treatment induced the expression of pre-tRNA Trp in total spleen cells, which might be related to neutrophil polarization and thus participated in the anti-tumour immunity mediated by IDO shRNA.…”

Section: Trnas and Immune Responsesmentioning

confidence: 99%

“…55 In the LLC1 lung cancer model, short hairpin against IDO (IDO shRNA) treatment induced the expression of pre-tRNA Trp in total spleen cells, which might be related to neutrophil polarization and thus participated in the anti-tumour immunity mediated by IDO shRNA. 56 In addition, host tRNAs are involved in various processes such as viral translation and reverse transcription, performing vital functions in regulating viral virulence and immunogenicity. Certain viruses, including human immunodeficiency virus type 1 (HIV-1), influenza A virus (IAV) and vaccinia virus (VV), have been reported to manipulate the tRNA pool of host cells to facilitate viral translation.…”

Section: Trnas and Immune Responsesmentioning

confidence: 99%

The tRNA‐associated dysregulation in immune responses and immune diseases

et al. 2019

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Transfer RNA (tRNA), often considered as a housekeeping molecule, mainly participates in protein translation by transporting amino acids to the ribosome. Nevertheless, accumulating evidence has shown that tRNAs are closely related to various physiological and pathological processes. The proper functioning of the immune system is the key to human health. The aim of this review is to investigate the relationships between tRNAs and the immune system. We detail the biogenesis and structure of tRNAs and summarize the pathogen tRNA-mediated infection and host responses. In addition, we address recent advances in different aspects of tRNA-associated dysregulation in immune responses and immune diseases, such as tRNA molecules, tRNA modifications, tRNA derivatives and tRNA aminoacylation. Therefore, tRNAs play an important role in immune regulation. Although our knowledge of tRNAs in the context of immunity remains, for the most part, unknown, this field deserves in-depth research to provide new ideas for the treatment of immune diseases. K E Y W O R D Sbiogenesis, immune diseases, immune responses, tRNA F I G U R E 1 The biogenesis and structure of tRNAs. tRNA: Transfer RNA; Pol III: RNA polymerase III; pre-tRNA: Precursor tRNA; mRNA: Messenger RNA; aaRS: Aminoacyl-tRNA synthetase; tsRNA: tRNA-derived small RNA; tRF: tRNA-derived fragment; tiRNA: tRNA-derived stress-induced RNA

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“…In spite of the Ki values, D-1-MT show higher antitumor activity in vivo in different tumors and combined therapy regimens. D-1-MT was more effective in reducing tumor mass in experimental models (Hou DY, et al, 2007; Liu K T, et al, 2016), and for that reason it is used in Phase 1 and 2 clinical trials with the commercial name of Indoximod ® (Tang SC, et al, 2016). Indoximod has been trial in mono and combined therapy to treat sarcoma, NSCLC, melanoma and colorectal cancer (Yentz S and Smith D, 2018).…”

Section: Introductionmentioning

confidence: 99%

1-Methyl-tryptophan enantiomers differently affect the cross-talking between mononuclear and tumor cells and interferon-γ production

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et al. 2019

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2The inhibition of the enzyme indoleamine-2,3-dioxygenase (IDO), that catalyzes the 3 oxidation of the amino acid tryptophan to kynurenine (KYN), is considered a good target 4 for immunoadjuvants in antineoplastic therapy. 1-Methyl-tryptophan (1-MT) is the most 5 studied molecule for this purpose. Although L-1-MT is better than D-1-MT in inhibiting 6 IDO, for an unknown reason the D-enantiomer has higher clinical efficacy. Here we took 7 advantage of co-cultures of tumor cells (SK-Mel 19 melanoma line; 1x10 5 cells/well) with 8 peripheral blood mononuclear cells (PBMC; 5x10 6 cells/well) to verify the effect of 1-9 MT enantiomers on cytokine production and tumoricidal activity. At a concentration that 10 did not affect KYN production, 1-MT (50 µM) affected the production of TNF-α, IL-10, 11 and IFN-γ measured in co-cultures supernatants. Stereospecificity was only observed for 12 IFN-γ production. D-1-MT inhibited more than 30% of IFN-γ production, while L-1-MT 13 had no effect. Stereospecific effect was also seen in PBMC tumoricidal activity, 14 estimated by tumor cell viability (Trypan assay). The racemic mixture DL-and D-1-MT 15 almost doubled the tumoricidal activity of PBMCs, while L-1-MT had no effect. These 16 are previous unknown off-target effects of D-1-MT. Our data suggest the modulation of 17 IFN-γ and the activation of tumor recognition and killing processes by immune cells as 18 important features for the in vivo effects of the D-1-MT. These findings should be 19 considered in future studies of immunoadjuvants for cancer treatment.20 21 22 Keyworks: D-1-methyl-tryptophan; indoleamine-2,3-dioxygenase; Indoximod; 23 interferon-gamma; immunomodulation; PBMC; TNF-; IL-10. 24 25

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Neutrophils are Essential in Short Hairpin RNA of Indoleamine 2,3- Dioxygenase Mediated-antitumor Efficiency

Cited by 7 publications

References 46 publications

Indoleamine 2,3‐dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma

Indoleamine 2,3‐dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma

The tRNA‐associated dysregulation in immune responses and immune diseases

1-Methyl-tryptophan enantiomers differently affect the cross-talking between mononuclear and tumor cells and interferon-γ production

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