Mesenchymal-Stromal Cell-like Melanoma-Associated Fibroblasts Increase IL-10 Production by Macrophages in a Cyclooxygenase/Indoleamine 2,3-Dioxygenase-Dependent Manner

Çakır, Uğur; Hajdara, Anna; Széky, Balázs; Mayer, Balázs; Kárpáti, Sarolta; Mezey, Éva; Silló, Pálma; Füredi, András; Pós, Zoltán; Érsek, Barbara; Sárdy, Miklós; Németh, Krisztián

doi:10.3390/cancers13246173

Cited by 8 publications

(9 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Enzyme activity can be calculated by (KYN/TRP) proportion. IDO act as main immunoregulator & transforms tryptophan into kynurenine, which causes cytotoxicity and apoptosis in tumor histology [15,16]. Indomethacin cox-2 inhibitor exhibited raised IDO1 inhibitory activity, which is beneficial for the malignant cells immunotherapy by suppressing interleukin-10 & prostaglandin E2 [19,20].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Anti-inflammatory Medication on Indoleamine 2,3 Dioxygenase Activity

Dawood

Bano²,

Sundus

et al. 2022

JPRI

View full text Add to dashboard Cite

Objective: To study the effects of anti-inflammatory medication on Indoleamine 2,3 dioxygenase activity. Research Design: This was an investigational study. Methodology: Eighteen fully grown albino rats separated into control and two treated sets, both treated sets were given indomethacin (50mg/1000g) orally. For acute treatment first treated set was sacrificed after 3.5 hrs & for chronic treatment second set was sacrificed after 3 days. However, control set animals were given an equivalent amount of vehicle. Results: Outcomes shows that serum Indoleamine 2,3 dioxygenase (IDO) enzyme activity was suppressed after acute treatment while serum IDO activity were increased after chronic treatment however no significant effect was seen on brain IDO. Conclusion: It is concluded that indomethacin has not shown any significant effect on brain IDO. But inhibits serum IDO activity.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Indoleamine 2,3-dioxygenase (IDO), enhances nitric oxide synthase liable for breakdown of tryptophan and arginine [14]. IDO act as main immunoregulator & transforms tryptophan into kynurenine, which causes cytotoxicity and apoptosis in tumor histology [15,16].…”

Section: Nsaidsmentioning

confidence: 99%

Effects of Anti-inflammatory Medication on Indoleamine 2,3 Dioxygenase Activity

Dawood

Bano²,

Sundus

et al. 2022

JPRI

View full text Add to dashboard Cite

show abstract

“…Both tumor cells and melanoma-associated fibroblasts (MAFs) produce COX-2 and IDO, inducing the expression of IL-10 in macrophages. Consequently, the pharmacological inhibition of COX-2 and IDO reverts the suppressive phenotype in macrophages ( 93 ). In addition, monocyte-derived macrophages induced by M-CSF upregulate IDO in response to IFN-γ or CD40L to deplete milieu tryptophan and suppress T cell responses to maintain peripheral tolerance ( 94 ).…”

Section: Metabolic Reprogramming In the Tmementioning

confidence: 99%

Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment

et al. 2023

View full text Add to dashboard Cite

The tumor microenvironment (TME) is a complex and constantly changing cellular system composed of heterogeneous populations of tumor cells and non-transformed stromal cells, such as stem cells, fibroblasts, endothelial cells, pericytes, adipocytes, and innate and adaptive immune cells. Tumor, stromal, and immune cells consume available nutrients to sustain their proliferation and effector functions and, as a result of their metabolism, produce a wide array of by-products that gradually alter the composition of the milieu. The resulting depletion of essential nutrients and enrichment of by-products work together with other features of the hostile TME to inhibit the antitumor functions of immune cells and skew their phenotype to promote tumor progression. This review briefly describes the participation of the innate and adaptive immune cells in recognizing and eliminating tumor cells and how the gradual metabolic changes in the TME alter their antitumor functions. In addition, we discuss the overexpression of the immune checkpoints and their ligands as a result of nutrient deprivation and by-products accumulation, as well as the amplification of the metabolic alterations induced by the immune checkpoints, which creates an immunosuppressive feedback loop in the TME. Finally, the combination of metabolic and immune checkpoint inhibitors as a potential strategy to treat cancer and enhance the outcome of patients is highlighted.

show abstract

“…Recently, our research group studied MAFs and showed that these cells suppress cytotoxic T lymphocyte activity [ 23 ]. We also found that, similarly to bone marrow mesenchymal stromal cells (BMSCs or MSCs), MAFs drive macrophages to produce IL-10, an anti-inflammatory cytokine that suppresses natural anti-cancer immunity [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Melanoma-Associated Fibroblasts (MAFs) with Activated γδ (Vδ2) T Cells: An In Vitro Cytotoxicity Model

Hajdara,

Çakır,

Érsek

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

The tumor microenvironment (TME) has gained considerable scientific attention by playing a role in immunosuppression and tumorigenesis. Besides tumor cells, TME is composed of various other cell types, including cancer-associated fibroblasts (CAFs or MAFs when referring to melanoma-derived CAFs) and tumor-infiltrating lymphocytes (TILs), a subpopulation of which is labeled as γδ T cells. Since the current anti-cancer therapies using γδ T cells in various cancers have exhibited mixed treatment responses, to better understand the γδ T cell biology in melanoma, our research group aimed to investigate whether activated γδ T cells are capable of killing MAFs. To answer this question, we set up an in vitro platform using freshly isolated Vδ2-type γδ T cells and cultured MAFs that were biobanked from our melanoma patients. This study proved that the addition of zoledronic acid (1–2.5 µM) to the γδ T cells was necessary to drive MAFs into apoptosis. The MAF cytotoxicity of γδ T cells was further enhanced by using the stimulatory clone 20.1 of anti-BTN3A1 antibody but was reduced when anti-TCR γδ or anti-BTN2A1 antibodies were used. Since the administration of zoledronic acid is safe and tolerable in humans, our results provide further data for future clinical studies on the treatment of melanoma.

show abstract

Mesenchymal-Stromal Cell-like Melanoma-Associated Fibroblasts Increase IL-10 Production by Macrophages in a Cyclooxygenase/Indoleamine 2,3-Dioxygenase-Dependent Manner

Cited by 8 publications

References 58 publications

Effects of Anti-inflammatory Medication on Indoleamine 2,3 Dioxygenase Activity

Effects of Anti-inflammatory Medication on Indoleamine 2,3 Dioxygenase Activity

Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment

Targeting Melanoma-Associated Fibroblasts (MAFs) with Activated γδ (Vδ2) T Cells: An In Vitro Cytotoxicity Model

Contact Info

Product

Resources

About