Targeting indoleamine-2,3-dioxygenase in cancer: Scientific rationale and clinical evidence

Ricciuti, Biagio; Leonardi, Giulia C.; Puccetti, Paolo; Fallarino, Francesca; Bianconi, Vanessa; Sahebkar, Amirhossein; Baglivo, Sara; Chiari, Rita; Pirro, Matteo

doi:10.1016/j.pharmthera.2018.12.004

Cited by 78 publications

(76 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IDO modifies inflammation and immunity through a variety of effector cells: induces the differentiation of Treg cells and apoptosis of effector T cells, prevents Treg cells destabilization and maintains the suppressive phenotype, recruits and activates MDSCs to suppress antitumor immune responses, inhibits the surface expression of activating receptors and regulates NK‐cell function . There is strong evidence that suppression of antitumor immune responses by IDO would make such catabolism an attractive target for therapeutic intervention …”

Section: Discussionmentioning

confidence: 99%

IDO and intra‐tumoral neutrophils were independent prognostic factors for overall survival for hepatocellular carcinoma

Wang

Yao

Zhang

et al. 2019

Clinical Laboratory Analysis

View full text Add to dashboard Cite

BackgroundBoth Indole‐amine‐2,3‐dioxygenase (IDO) and neutrophils were proved to have pro‐tumor effect in some kinds of solid tumors by immune suppression. However, little is known about their effect on hepatocellular carcinoma (HCC) and the relationship between these two immune‐suppressive factors. The aim of this study was to evaluate the prognostic significance of IDO and intra‐tumoral neutrophils and their correlations in HCC.MethodsSpecimens’ tissue microarray (TMA) for 153 HCC patients was used in this study. We examined intra‐tumoral expression of IDO and CD66b in TMA. The Kaplan‐Meier method and Cox regression models were used to evaluate the prognostic value of IDO expression and CD66b.ResultsMultivariate analysis showed both IDO expression and intra‐tumoral neutrophils infiltration were independent prognostic factors for overall survival (OS). In high IDO expression group, the percentage of intra‐tumoral neutrophils infiltration was higher than that in low IDO expression group.ConclusionBoth IDO and intra‐tumoral neutrophils were independent prognostic factors for overall survival for HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

IDO and intra‐tumoral neutrophils were independent prognostic factors for overall survival for hepatocellular carcinoma

Wang

Yao

Zhang

et al. 2019

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

“…Immune checkpoints are inhibitory pathways responsible for regulating the immune responses to avoid excessive immune activity and keep the central and peripheral tolerance . Monoclonal antibodies designed to block such immune checkpoints are known as immune checkpoint blockers, reestablish the tumor‐specific cellular immune responses against the cancerous cells …”

Section: Prospects In Adoptive Cell Transfermentioning

confidence: 99%

“…Although some studies reported some levels of toxicity in some cases, promising results have been obtained representing a noticeable response rate in several cancer types. The enhancement of cellular response through the increment of CD 8+ T cells inside the tumor has been suggested as one of the possible mechanisms underlying the anticancer ability of IDO blockade …”

Section: Prospects In Adoptive Cell Transfermentioning

confidence: 99%

“…107 Monoclonal antibodies designed to block such immune checkpoints are known as immune checkpoint blockers, reestablish the tumor-specific cellular immune responses against the cancerous cells. 108 There is growing evidence that monoclonal antibody therapy using anti-CTLA-4, programmed death-1, and CD137 (4-1BB) monoclonal antibodies can enhance antitumor immunity. 109 Studies on patients with metastatic melanoma have shown that antibody therapy with anti-CTLA-4 antibodies could induce melanoma regression and improve overall patient survival.…”

Section: Prospects In Adoptive Cell Transfermentioning

confidence: 99%

“…As noted above, the IDO enzyme present in the macrophages and DCs takes part in the tryptophan catabolism producing kynurenines and their derivatives leading to restriction of cellular response through T-cell proliferation disruption and induction of Treg and myeloid-derived suppressor cells differentiation increment. 108 Tryptophan degradation is one of the main pathways involved in the immune resistance from which cancer cells take advantage. 93 Hence, the IDO blockade has gained much attention as a cancer therapy option.…”

Section: Prospects In Adoptive Cell Transfermentioning

confidence: 99%

See 2 more Smart Citations

Cell transfer‐based immunotherapies in cancer: A review

et al. 2019

Self Cite

View full text Add to dashboard Cite

In cell transfer therapy (CTT), immune cells such as innate immune‐derived natural killer cells and dendritic cells as well as acquired immune‐related T lymphocytes such as tumor‐infiltrating lymphocytes and cytokine‐activated or genetically modified peripheral blood T cells are used in the management of cancer. These therapies are increasingly becoming the most used treatment modality in cancer after tumor resection, chemotherapy, and radiotherapy. In adoptive cell transfer, the lymphocytes isolated from either a donor or the patient are modified ex vivo and reinfused to target malignant cells. Transferring in vitro‐manipulated immune cells produces a continuous antitumor immune response. In this review, we evaluate the recent advances in CTT for the management of various malignancies.

show abstract

Immuno‐Oncology

Buesking

Mayes

Combs

2021

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

The ability to avoid immune surveillance and destruction is one of the hallmarks of cancer. Identification of ligands that can prevent immune cells from killing malignant cells was the pivotal discovery for which the 2018 Nobel Prize in Medicine was awarded and initiated the current era in cancer immunotherapy. As a result, a number of antibody‐based approaches including checkpoint inhibitors and bispecific antibodies have been explored. More recently, small molecule drugs have emerged as a complementary approach. Small molecules can offer unique advantages over antibody therapies including access to intracellular targets, opportunities for oral dosing, higher relative exposures in the brain, and increased penetration into tumors. This article provides a brief overview of antibody approaches and then summarizes nine immuno‐oncology targets for which small molecule modulators have been described in the peer‐review literature.

show abstract

Targeting indoleamine-2,3-dioxygenase in cancer: Scientific rationale and clinical evidence

Cited by 78 publications

References 113 publications

IDO and intra‐tumoral neutrophils were independent prognostic factors for overall survival for hepatocellular carcinoma

IDO and intra‐tumoral neutrophils were independent prognostic factors for overall survival for hepatocellular carcinoma

Cell transfer‐based immunotherapies in cancer: A review

Immuno‐Oncology

Contact Info

Product

Resources

About