The correlations between IL-17 vs. Th17 cells and cancer patient survival: a systematic review

Punt, Simone; Langenhoff, J.M.; Putter, Hein; Fleuren, Gert Jan; Gorter, Arko; Jordanova, Ekaterina S.

doi:10.4161/2162402x.2014.984547

Cited by 104 publications

(84 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, knocking down BATF3 in Th2 cells dramatically decreased expression of IL4 and IL10 cytokines (41, 42). This is an intriguing biological connection as both the overexpression of IL10 and elevated levels of Th17 cells in peripheral blood were correlated with improved cancer patient survival in previous studies (43, 44). These findings therefore align with our observations that minor T allele carriers of germline eQTL rs6695772, associated with worse OS, express low levels of BATF3 which may in turn down-regulate IL4 and IL10 .…”

Section: Discussionmentioning

confidence: 67%

The Expression Quantitative Trait Loci in Immune Pathways and their Effect on Cutaneous Melanoma Prognosis

Vogelsang

Martínez

Rendleman

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose The identification of personalized germline markers with biological relevance for the prediction of cutaneous melanoma (CM) prognosis is highly demanded but to date it has been largely unsuccessful. As melanoma progression is controlled by host immunity, here we present a novel approach interrogating immunoregulatory pathways using the genome-wide maps of expression quantitative trait loci (eQTL) to reveal biologically relevant germline variants modulating CM outcomes. Experimental Design Using whole genome eQTL data from a healthy population, we identified 385 variants -significantly impacting the expression of 268 immune-relevant genes. The 40 most significant eQTLs were tested in a prospective cohort of 1,221 CM patients for their association with overall (OS) and recurrence-free survival using Cox regression models. Results We identified highly significant associations with better melanoma OS for rs6673928, impacting IL19 expression (HR 0.56, 95%CI 0.41–0.77; P=0.0002) and rs6695772, controlling the expression of BATF3 (HR 1.64, 95%CI 1.19–2.24; P=0.0019). Both associations map in the previously suspected melanoma prognostic locus at 1q32. Furthermore, we show that their combined effect on melanoma OS is substantially enhanced reaching the level of clinical applicability (HR 1.92, 95%CI 1.43–2.60; P=2.38e–5). Conclusions Our unique approach of interrogating lymphocyte-specific eQTLs reveals novel and biologically relevant immunomodulatory eQTL predictors of CM prognosis that are independent of current histopathological markers. The significantly enhanced combined effect of identified eQTLs suggests the personalized utilization of both SNPs in a clinical setting, strongly indicating the promise of the proposed design for the discovery of prognostic or risk germline markers in other cancers.

show abstract

Section: Discussionmentioning

confidence: 67%

The Expression Quantitative Trait Loci in Immune Pathways and their Effect on Cutaneous Melanoma Prognosis

Vogelsang

Martínez

Rendleman

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Altogether our data reveal a positive contribution of Th17 cells to beneficial antitumour immune responses developing in CRC and underline their pleiotropic function resulting from the production of a broad spectrum of cytokines and chemokines beyond IL- 17. This may, at least partially, explain the discrepancies between results obtained from studies evaluating the effects of IL-17 or IL-17 signalling only and those examining functions of the whole Th17 cell subset. [47][48][49][50] Our findings have important clinical implications. Indeed, the positive contribution of Th17 to anti-tumour immune responses should not be disregarded when developing new IL-17/Th17 targeted treatments in CRC, possibly resulting in impaired tumour infiltration by beneficial effector cells.…”

Section: Discussionmentioning

confidence: 68%

Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer

Amicarella

Muraro

Hirt

et al. 2015

Gut

152

131

View full text Add to dashboard Cite

BackgroundThe immune contexture predicts prognosis in human colorectal cancer (CRC). Whereas tumour-infiltrating CD8+ T cells and myeloid CD16+ myeloperoxidase (MPO)+ cells are associated with favourable clinical outcome, interleukin (IL)-17-producing cells have been reported to correlate with severe prognosis. However, their phenotypes and functions continue to be debated.ObjectiveTo investigate clinical relevance, phenotypes and functional features of CRC-infiltrating, IL-17-producing cells.MethodsIL-17 staining was performed by immunohistochemistry on a tissue microarray including 1148 CRCs. Phenotypes of IL-17-producing cells were evaluated by flow cytometry on cell suspensions obtained by enzymatic digestion of clinical specimens. Functions of CRC-isolated, IL-17-producing cells were assessed by in vitro and in vivo experiments.ResultsIL-17+ infiltrates were not themselves predictive of an unfavourable clinical outcome, but correlated with infiltration by CD8+ T cells and CD16+ MPO+ neutrophils. Ex vivo analysis showed that tumour-infiltrating IL-17+ cells mostly consist of CD4+ T helper 17 (Th17) cells with multifaceted properties. Indeed, owing to IL-17 secretion, CRC-derived Th17 triggered the release of protumorigenic factors by tumour and tumour-associated stroma. However, on the other hand, they favoured recruitment of beneficial neutrophils through IL-8 secretion and, most importantly, they drove highly cytotoxic CCR5+CCR6+CD8+ T cells into tumour tissue, through CCL5 and CCL20 release. Consistent with these findings, the presence of intraepithelial, but not of stromal Th17 cells, positively correlated with improved survival.ConclusionsOur study shows the dual role played by tumour-infiltrating Th17 in CRC, thus advising caution when developing new IL-17/Th17 targeted treatments.

show abstract

“…Although our results were limited to peripheral circulating samples, an MDSC-IL-17-VEGF axis seems to be present in patients with gastric and colorectal cancers, and, more importantly, this axis seems to be closely related to cancerrelated systemic infl ammation, immune suppression, and nutritional impairment. With regard to prognosis, expressions of VEGF and IL-17 are reported to be independent significant prognostic factors in patients with various cancers 20,21,27,28) . In the present study, we also confi rmed that worse prognoses was signifi cantly observed in both stage III and IV gastric and colorectal cancers for patients exhibiting high production of IL-17 or high serum levels of VEGF than those having low levels of IL-17 or VEGF.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it has been reported that IL-17 induces VEGF-A expression via signal transducer and activator of transcription (STAT)-3 signaling mechanisms 27,28) . MDSCs have been reported to express receptors for VEGF-A and be activated by VEGF-A, and distribution of Treg cell may also increase through MDSC-associated mechanisms 25,26) .…”

Section: Discussionmentioning

confidence: 99%

IL-17 and VEGF are significantly associated with disease progression involving systemic inflammation in patients with gastric and colorectal cancers

Minamikawa

Shibata

Gonda

et al. 2017

Ann. Cancer Res. Therap.

View full text Add to dashboard Cite

Gastric and colorectal cancers are leading causes of death worldwide. Although a relationship between inflammation and the innate immunity in cancer-bearing hosts is widely accepted, the precise cell mechanisms mediating this relationship have not been elucidated. The aim of this study was to investigate the status of systemic inflammation, immune suppression, malnutrition, and prognosis associated with interleukin (IL)-17 and vascular endothelial growth factor (VEGF) in patients with gastric and colorectal cancers.The production of IL-17 and the serum levels of VEGF in patients with gastric and colorectal cancers were up-regulated in advanced stages of the diseases, which were positively correlated with the levels of myeloid-derived suppressor cells, the neutrophil-to-lymphocyte ratio, and C-reactive protein, while both were inversely correlated with IL-12 production, stimulation index, and nutritional markers including prealbumin and retinol binding protein. Overall survival of patients with stage III and IV gastric or colorectal cancer was significantly worse for patients with high IL-17 production or high VEGF levels than for those with low IL-17 production or low VEGF levels. The observations in the present study suggest that IL-17 and VEGF are closely associated with disease progression, and may serve as useful markers of the immune suppression, malnutrition, and prognosis in patients with gastric and colorectal cancers.

show abstract

The correlations between IL-17 vs. Th17 cells and cancer patient survival: a systematic review

Cited by 104 publications

References 79 publications

The Expression Quantitative Trait Loci in Immune Pathways and their Effect on Cutaneous Melanoma Prognosis

The Expression Quantitative Trait Loci in Immune Pathways and their Effect on Cutaneous Melanoma Prognosis

Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer

IL-17 and VEGF are significantly associated with disease progression involving systemic inflammation in patients with gastric and colorectal cancers

Contact Info

Product

Resources

About