Indoleamine 2,3-dioxygenase (Ido) inhibitors and their nanomedicines for cancer immunotherapy

Guo, Yixuan; Liu, Yu; Wu, Wei; Ling, Daishun; Zhang, Qiao; Zhao, Peng; Hu, Xi

doi:10.1016/j.biomaterials.2021.121018

Cited by 79 publications

(47 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, greater amounts of calreticulin (CRT) are expressed on the surface of tumor cells, apoptotic cells, and some drug‐treated cells compared to normal cells; this compound mainly exists in the endoplasmic reticulum as a class of calcium‐binding proteins. [ 42 ] It will be transported to the cell surface when the endoplasmic reticulum is stressed, and CRT on the cell surface can bind to the receptors on the surface of some immune cells, such as macrophages, dendritic cells and other immune cells. [ 43 ] It can stimulate macrophages and immature DCs in the body to stimulate dying tumor cells and their fragments, thereby enhancing the immune response to these cells.…”

Section: Resultsmentioning

confidence: 99%

A “Closed‐Loop” Therapeutic Strategy Based on Mutually Reinforced Ferroptosis and Immunotherapy

Zhang

Yang

et al. 2022

Adv Funct Materials

134

View full text Add to dashboard Cite

The immunosuppression and immune escape of current immunotherapy result in low efficacy, and ferroptosis is greatly restricted by the low reactive oxygen species (ROS) production efficiency. Here, for the first time a “closed‐loop” therapy based on photothermal enhancement of ferroptosis and immunotherapy stimulated by each other on a multifunctional nanoplatform is reported. This platform is composed of copper silicate and iron silicate mesoporous hollow nanospheres, followed by in situ growth of Au nanoparticles and loading of an immune adjuvant resiquimod R848. The laser irradiation‐mediated heat and the introduction of copper ions significantly enhance ROS generation, leading to the simultaneous depletion of glutathione peroxidase 4 (GPX4) and glutathione (GSH). The onset of ferroptosis in tumor cells is thus enhanced and an immune response with immunogenic cell death (ICD) is triggered, promoting the dendritic cells (DCs) maturation and T cell infiltration. Interferon γ (IFN‐γ) released from CD8+ T cells downregulates the expression of SLC7A11 and GPX4, which in turn enhances ferroptosis expression, thus constituting a “closed‐Loop” therapy. Importantly, this system is effective in both killing the primary tumor and inhibiting tumor metastasis. The proposed “closed‐loop” therapeutic strategy may provide a guidance for the design of future antitumor nanoplatforms.

show abstract

Section: Resultsmentioning

confidence: 99%

A “Closed‐Loop” Therapeutic Strategy Based on Mutually Reinforced Ferroptosis and Immunotherapy

Zhang

Yang

et al. 2022

Adv Funct Materials

134

View full text Add to dashboard Cite

show abstract

“…Thus, considering the remarkable immunosuppressive effect of ICOS, an anti-ICOS antagonist might be more appropriate in glioma; however, this requires a further in-depth understanding of the mechanism of ICOS. Meanwhile, IDO1, a metabolic modulator reported to promote tumors develop immunotherapy resistance (51), has also been identified as an immune target, and the evaluation of anti-IDO1 is undergoing(52). ICOS showed a strong correlation with these molecules, providing more evidence for immunotherapy combination for gliomas.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, IDO1, a metabolic modulator reported to promote tumors develop immunotherapy resistance (51), has also been identified as an immune target, and the evaluation of anti-IDO1 is undergoing (52). ICOS showed a strong correlation with these molecules, providing more evidence for immunotherapy combination for gliomas.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profile and clinical characterization of ICOS expression in brain gliomas

Wang

Shi

Shan

2022

Preprint

View full text Add to dashboard Cite

Aims: Inducible Co-Stimulator (ICOS), an immune costimulatory molecule, has been found to play an essential role across various malignancies. This study investigated the transcriptome profile and clinical characterization of ICOS in gliomas. Methods: Clinical information and transcriptome data of 301 glioma samples were downloaded from the Chinese Glioma Genome Atlas (CGGA) data set for analysis. Furthermore, the results were validated in 697 samples with RNAseq data from the TCGA glioma data set. In addition, single-cell sequencing data from CGGA and GSE 163108 datasets were used to analyze the ICOS expression across different cell types. Statistical analyses and figure production were performed with R-language. Results: We found that ICOS was significantly upregulated in higher-grade, IDH wildtype, and mesenchymal subtype of gliomas. Functional enrichment analyses revealed that ICOS was mainly involved in glioma-related immune response. Moreover, ICOS showed a robust correlation with other immune checkpoints, including PD1/PD-L1/PD-L2 pathway, CTLA4, ICOSL (ICOS ligand), and IDO1. Furthermore, based on seven clusters of metagenes, GSVA identified that ICOS was tightly associated with HCK, LCK, MHC-I, MHC-II, STAT1, and interferon, especially with LCK, suggesting a strong correlation between ICOS and T-cell activity in gliomas. In cell lineage analysis, ICOS-higher gliomas tended to recruit dendritic cells, monocytes, and macrophages into the tumor microenvironment. Single-cell sequencing analysis indicated that ICOS was highly expressed by regulatory T cells (Treg). Finally, patients with higher ICOS had shortened survival. ICOS was an independent prognosticator for glioma patients. Conclusions: Higher ICOS was correlated with more malignancy of gliomas and significantly associated with Treg activity among glioma-related immune responses. Moreover, ICOS could contribute as an independent prognostic factor for gliomas. Our study highlighted the role of ICOS in glioma and may facilitate therapeutic strategies targeting ICOS for glioma.

show abstract

“…Therefore, the targeted blockade of IDO1 or IDO1-driven metabolism pathway represents a promising therapeutic pathway. Meanwhile, IDO1 inhibitors combined with other therapies should be considered as an effective strategy in tumor immunotherapy, such as effectively suppressing tumor growth by synergizing photothermal therapy (PTT), radiotherapy, or chemotherapy ( 110 – 112 ). With the discovery of cancer tissue expression IDO1 or TDO or both, IDO1/TDO combined inhibitors have become a study focus ( 113 – 115 ).…”

Section: The Significance Of Targeting Indoleamine 23-dioxygenase 1 In Tumor Therapymentioning

confidence: 99%

Indoleamine 2,3-Dioxygenase 1: A Promising Therapeutic Target in Malignant Tumor

Song

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Tumorigenesis is a complex multifactorial and multistep process in which tumors can utilize a diverse repertoire of immunosuppressive mechanisms to evade host immune attacks. The degradation of tryptophan into immunosuppressive kynurenine is considered an important immunosuppressive mechanism in the tumor microenvironment. There are three enzymes, namely, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1), and indoleamine 2,3-dioxygenase 2 (IDO2), involved in the metabolism of tryptophan. IDO1 has a wider distribution and higher activity in catalyzing tryptophan than the other two; therefore, it has been studied most extensively. IDO1 is a cytosolic monomeric, heme-containing enzyme, which is now considered an authentic immune regulator and represents one of the promising drug targets for tumor immunotherapy. Collectively, this review highlights the regulation of IDO1 gene expression and the ambivalent mechanisms of IDO1 on the antitumoral immune response. Further, new therapeutic targets via the regulation of IDO1 are discussed. A comprehensive analysis of the expression and biological function of IDO1 can help us to understand the therapeutic strategies of the inhibitors targeting IDO1 in malignant tumors.

show abstract

Indoleamine 2,3-dioxygenase (Ido) inhibitors and their nanomedicines for cancer immunotherapy

Cited by 79 publications

References 122 publications

A “Closed‐Loop” Therapeutic Strategy Based on Mutually Reinforced Ferroptosis and Immunotherapy

A “Closed‐Loop” Therapeutic Strategy Based on Mutually Reinforced Ferroptosis and Immunotherapy

Transcriptome profile and clinical characterization of ICOS expression in brain gliomas

Indoleamine 2,3-Dioxygenase 1: A Promising Therapeutic Target in Malignant Tumor

Contact Info

Product

Resources

About