The prognostic significance of indoleamine-2,3-dioxygenase and the receptors for transforming growth factor β and interferon γ in metastatic lymph nodes in malignant melanoma

Pelak, M.; Śnietura, Mirosław; Lange, Dariusz; Nikiel, Barbara; Pecka, Katarzyna M.

doi:10.5114/pjp.2015.57249

Cited by 14 publications

(11 citation statements)

References 28 publications

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“…This study demonstrates that IDO activity at baseline is an important prognostic marker for patients with NSCLC treated with fractionated RT. This is in agreement with previous studies that baseline IDO immune status plays a prognostic role after surgery or chemotherapy (16,17,20-22). Our data demonstrated low activity of IDO, i.e.…”

Section: Discussionsupporting

confidence: 93%

IDO Immune Status after Chemoradiation May Predict Survival in Lung Cancer Patients

et al. 2018

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Host immunity influences the impact of radiotherapy (RT) in cancer, but mechanistic connections remain obscure. In this study, we investigated the relationship of indoleamine 2,3-dioxygenase (IDO) systemic activity on clinical outcomes in RT-treated non-small cell lung cancer (NSCLC). IDO-mediated production of kynurenine and the kynurenine:tryptophan ratio in patient blood serum were determined for stage III NSCLC patients at times before, during, and after RT administration and then correlated to overall survival (OS), progression-free survival, and disease progression rate in patients. We found the impact of RT on these serum IDO markers to be heterogeneous in patients. On average, kynurenine:tryptophan ratios were reduced during RT but restored after RT. Notably, both baseline levels of kynurenine:tryptophan and changes in the levels of kynurenine after RT were significantly associated with OS. When combined, favorable change and favorable baseline corresponded with very long-term OS (median OS was not reached after 57 months of median follow-up). Favorable change combined with unfavorable baseline still corresponded with a lack of distant metastases. Our results suggest that RT alters IDO-mediated immune status in NSCLC patients and that changes in this serum biomarker may be useful to predict outcomes and perhaps personalize RT dosage to improve survival. Radiotherapy appears to influence systemic IDO activity and to exert a significant impact on metastatic risk and overall survival, with possible implications for defining a biomarker to optimize radiation dose in patients to improve outcomes. .

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Section: Discussionsupporting

confidence: 93%

IDO Immune Status after Chemoradiation May Predict Survival in Lung Cancer Patients

et al. 2018

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“…For example, Rubel et al found that high amounts of both IDO+ melanoma and stromal cells correlate with poor progression-free survival (PFS), and high amounts of IDO+ melanoma cells were also positively associated with Breslow’s depth [ 13 ]. In another study, abundance of IDO-expressing melanoma cells in LNMs of CM was associated with poor OS [ 14 ]. Similarly, our results indicate that IDO expression in both stromal immune cells and tumor cells promote tumorigenesis in CM, as the number of both IDO+ stromal immune cells and IDO+ tumor cells was significantly higher in malignant compared with benign lesions.…”

Section: Discussionmentioning

confidence: 99%

The role of FoxP3+ regulatory T cells and IDO+ immune and tumor cells in malignant melanoma – an immunohistochemical study

et al. 2021

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Background FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) participate in the formation of an immunosuppressive tumor microenvironment (TME) in malignant cutaneous melanoma (CM). Recent studies have reported that IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. Methods We investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases (LNMs) of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells, and the coverage and intensity of IDO+ tumor cells were analysed. Results The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence˗free survival. We further showed that there was a positive correlation between IDO+ tumor cells and FoxP3+ Tregs. Conclusions These results indicate that IDO is strongly involved in melanoma progression. FoxP3+ Tregs also seems to contribute to the immunosuppressive TME in CM, but their significance in melanoma progression remains unclear. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies.

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“…High levels of IDO have been reported in melanoma (Brody et al, 2009), PDA (Witkiewicz et al, 2009) and ovarian cancer (Inaba et al, 2009) as well as many other tumors (Wainwright et al, 2012). IDO is associated with reduced CD8 T cell infiltration and poor patient survival (Pelak et al, 2015; Speeckaert et al, 2012). IDO promotes peritoneal dissemination of ovarian cancer cells by promoting angiogenesis and generating a tolerogenic environment that suppresses anti-tumor immune responses by NK cells and T cells (Tanizaki et al, 2014; Wang et al, 2012).…”

Section: Metabolic Challenges In the Tme: Impact On T Lymphocytes Andmentioning

confidence: 99%

Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies

2017

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T cell dysfunction in solid tumors results from multiple mechanisms. Altered signaling pathways in tumor cells help produce a suppressive tumor microenvironment enriched for inhibitory cells, posing a major obstacle for cancer immunity. Metabolic constraints to cell function and survival shape tumor progression and immune cell function. In the face of persistent antigen, chronic T cell receptor signaling drives T lymphocytes to a functionally exhausted state. Here we discuss how the tumor and its microenvironment influences T cell trafficking and function with a focus on melanoma, pancreatic and ovarian cancer, and discuss how scientific advances may help overcome these hurdles.

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The prognostic significance of indoleamine-2,3-dioxygenase and the receptors for transforming growth factor β and interferon γ in metastatic lymph nodes in malignant melanoma

Cited by 14 publications

References 28 publications

IDO Immune Status after Chemoradiation May Predict Survival in Lung Cancer Patients

IDO Immune Status after Chemoradiation May Predict Survival in Lung Cancer Patients

The role of FoxP3+ regulatory T cells and IDO+ immune and tumor cells in malignant melanoma – an immunohistochemical study

Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies

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