IDO blockade negatively regulates the CTLA-4 signaling in breast cancer cells

Azimnasab-Sorkhabi, Parviz; Soltani-Asl, Maryam; Yoshinaga, Túlio Teruo; Massoco, Cristina de Oliveira; Kfoury, José Roberto

doi:10.1007/s12026-023-09378-0

Cited by 6 publications

(3 citation statements)

References 36 publications

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“…Numerous studies have underscored the key regulatory roles of lncRNAs in tumors and the immune system. Notably, increased expression of the immune checkpoint protein IDO1 negatively regulates the expression of CTLA-4, both known to modulate antitumor immune responses [ 63 ]. The combined effect of these molecular alterations suggests potential tumor survival mechanisms, including immune evasion and dysregulation of G1/S DNA damage [ 64 ] contributing to moderate residual disease.…”

Section: Resultsmentioning

confidence: 99%

Advancing drug-response prediction using multi-modal and -omics machine learning integration (MOMLIN): a case study on breast cancer clinical data

Rashid,

Selvarajoo

2024

Briefings in Bioinformatics

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The inherent heterogeneity of cancer contributes to highly variable responses to any anticancer treatments. This underscores the need to first identify precise biomarkers through complex multi-omics datasets that are now available. Although much research has focused on this aspect, identifying biomarkers associated with distinct drug responders still remains a major challenge. Here, we develop MOMLIN, a multi-modal and -omics machine learning integration framework, to enhance drug-response prediction. MOMLIN jointly utilizes sparse correlation algorithms and class–specific feature selection algorithms, which identifies multi-modal and -omics–associated interpretable components. MOMLIN was applied to 147 patients’ breast cancer datasets (clinical, mutation, gene expression, tumor microenvironment cells and molecular pathways) to analyze drug-response class predictions for non-responders and variable responders. Notably, MOMLIN achieves an average AUC of 0.989, which is at least 10% greater when compared with current state-of-the-art (data integration analysis for biomarker discovery using latent components, multi-omics factor analysis, sparse canonical correlation analysis). Moreover, MOMLIN not only detects known individual biomarkers such as genes at mutation/expression level, most importantly, it correlates multi-modal and -omics network biomarkers for each response class. For example, an interaction between ER-negative-HMCN1-COL5A1 mutations-FBXO2-CSF3R expression-CD8 emerge as a multimodal biomarker for responders, potentially affecting antimicrobial peptides and FLT3 signaling pathways. In contrast, for resistance cases, a distinct combination of lymph node-TP53 mutation-PON3-ENSG00000261116 lncRNA expression-HLA-E-T-cell exclusions emerged as multimodal biomarkers, possibly impacting neurotransmitter release cycle pathway. MOMLIN, therefore, is expected advance precision medicine, such as to detect context–specific multi-omics network biomarkers and better predict drug-response classifications.

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Section: Resultsmentioning

confidence: 99%

Advancing drug-response prediction using multi-modal and -omics machine learning integration (MOMLIN): a case study on breast cancer clinical data

Rashid,

Selvarajoo

2024

Briefings in Bioinformatics

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“…Also, in triple-negative breast cancer, the expression of IDO1 has an association with forkhead box P3 (FoxP3) positive cells [ 65 ]. Interestingly, it is suggested that IDO1 blocking might interrupt CTLA-4 signaling in breast cancer cells [ 66 ]. Specifically, in colorectal cancer IDO1 activates the phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) pathway that promotes tumor progression [ 67 ].…”

Section: Ido Expresses In Various Cancer Typesmentioning

confidence: 99%

Indoleamine-2,3 dioxygenase: a fate-changer of the tumor microenvironment

et al. 2023

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Indoleamine-2,3 dioxygenase is a rate-limiting enzyme in the tryptophan catabolism in kynurenine pathways that has an immunosuppressive effect and supports cancer cells to evade the immune system in different cancer types. Diverse cytokines and pathways upregulate the production of indoleamine-2,3 dioxygenase enzymes in the tumor microenvironment and cause more production and activity of this enzyme. Ultimately, this situation results in anti-tumor immune suppression which is in favor of tumor growth. Several inhibitors such as 1-methyl-tryptophan have been introduced for indoleamine-2,3 dioxygenase enzyme and some of them are widely utilized in pre-clinical and clinical trials. Importantly at the molecular level, indoleamine-2,3 dioxygenase is positioned in a series of intricate signaling and molecular networks. Here, the main objective is to provide a focused view of indoleamine-2,3 dioxygenase enhancer pathways and propose further studies to cover the gap in available information on the function of indoleamine-2,3 dioxygenase enzyme in the tumor microenvironment.

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“…Azimnasab-Sorkhabi et al. performed in vitro experiments to demonstrate the effect of anti-CTLA-4 antibody on the migratory and clonogenic capacity of mouse mammary tumor cells ( 24 ). In a study by Pruitt et al., the transfection of anti-CTLA-4 antibody into DCs enhanced the activity of cytotoxic T lymphocytes (CTLs), which contributed to the inhibition of breast cancer cell growth ( 25 ).…”

Section: Ctla-4 Inhibitor Monotherapymentioning

confidence: 99%

Recent research and clinical progress of CTLA-4-based immunotherapy for breast cancer

Zhang,

Mi,

Xin

et al. 2023

Front. Oncol.

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Breast cancer is characterized by a high incidence rate and its treatment challenges, particularly in certain subtypes. Consequently, there is an urgent need for the development of novel therapeutic approaches. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) is currently gaining momentum for the treatment of breast cancer. Substantial progress has been made in clinical studies employing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors for breast cancer, but the cure rates are relatively low. To improve the efficacy of CTLA-4-based therapy for breast cancer, further research is imperative to explore more effective immune-based treatment strategies. In addition to monotherapy, CTLA-4 inhibitors are also being investigated in combination with other ICIs or alternative medications. However, it should be noted that immune-based treatments may cause adverse events. This review focuses on the mechanisms of CTLA-4 inhibitor monotherapy or combination therapy in breast cancer. We systematically summarize the latest research and clinical advances in CTLA-4-based immunotherapy for breast cancer, providing new perspectives on the treatment of breast cancer. In addition, this review highlights the immune-related adverse events (irAEs) associated with CTLA-4 inhibitors, providing insights into the development of appropriate clinical tumor immunotherapy regimens and intervention strategies.

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IDO blockade negatively regulates the CTLA-4 signaling in breast cancer cells

Cited by 6 publications

References 36 publications

Advancing drug-response prediction using multi-modal and -omics machine learning integration (MOMLIN): a case study on breast cancer clinical data

Advancing drug-response prediction using multi-modal and -omics machine learning integration (MOMLIN): a case study on breast cancer clinical data

Indoleamine-2,3 dioxygenase: a fate-changer of the tumor microenvironment

Recent research and clinical progress of CTLA-4-based immunotherapy for breast cancer

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