Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer

Goode, Ellen L.; DeRycke, Melissa S.; Kalli, Kimberly R.; Oberg, Ann L.; Cunningham, Julie M.; Maurer, Mathew S.; Fridley, Brooke L.; Armasu, Sebastian M.; Serie, Daniel J.; Ramar, Priya; Goergen, Krista M.; Vierkant, Robert A.; Rider, David N.; Sicotte, Hugues; Wang, Chen; Winterhoff, Boris; Phelan, Catherine M.; Schildkraut, Joellen M.; Weber, Rachel Palmieri; Iversen, Ed; Berchuck, Andrew; Sutphen, Rebecca; Birrer, Michael J.; Hampras, Shalaka S.; Preus, Leah; Gayther, Simon A.; Ramus, Susan J.; Wentzensen, Nicolas; Yang, Hannah; Song, Honglin; Tyrer, Jonathan P.; Pharoah, Paul; Konecny, Gottfried E.; Sellers, Thomas A.; Ness, Roberta B.; Sucheston, Lara; Odunsi, Kunle; Hartmann, Lynn C.; Moysich, Kirsten B.; Knutson, Keith L.

doi:10.1371/journal.pone.0053903

Cited by 21 publications

(24 citation statements)

References 53 publications

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“…We recently analyzed expression quantitative trait loci (eQTL) and sequence-based tagging single nucleotide polymorphisms (tagSNPs) for 79 Treg associated genes in invasive ovarian cancer cases. We found that poorer survival was associated with minor alleles at SNPs in TNFRSF18 (OX40) in the mucinous subtype, in CD80 in the endometrioid subtype, CD25 in endometrioid subtype, and CTLA4 in the clear cell subtype [156, 157]. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of immune cells, these results suggest the need for follow-up phenotypic studies and suggest that the role of the immune system may differ among the various subtypes of cancer.…”

Section: Novel Targets Identified By Analysis Of Genetic Variationmentioning

confidence: 99%

RETRACTED ARTICLE: Targeted immune therapy of ovarian cancer

Knutson

Karyampudi

Lamichhane

et al. 2014

Cancer Metastasis Rev

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Clinical outcomes, such as recurrence free survival and overall survival, in ovarian cancer are quite variable, independent of common characteristics such as stage, response to therapy and grade. This disparity in outcomes warrants further exploration and therapeutic targeting into the interaction between the tumor and host. One compelling host characteristic that contributes both to the initiation and progression of ovarian cancer is the immune system. Hundreds of studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease. Recent studies also show that anti-tumor immunity is often negated by immune regulatory cells present in the tumor microenvironment. Regulatory immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological targets that influence ovarian cancer outcome as well as include an update on newer immunotherapeutic strategies.

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Section: Novel Targets Identified By Analysis Of Genetic Variationmentioning

confidence: 99%

RETRACTED ARTICLE: Targeted immune therapy of ovarian cancer

Knutson

Karyampudi

Lamichhane

et al. 2014

Cancer Metastasis Rev

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“…RNA extracted from fresh frozen tumors was assessed using Agilent Whole Human Genome 4x44K Expression Arrays as previously described (4, 12). Batch-effects among two different RNA preparations and three microarray profiling dates were corrected to adjust Cy5, Cy3 labeling differences observed among experimental batches (4, 12).…”

Section: Methodsmentioning

confidence: 99%

Pooled Clustering of High-Grade Serous Ovarian Cancer Gene Expression Leads to Novel Consensus Subtypes Associated with Survival and Surgical Outcomes

Wang

Armasu

Kalli

et al. 2017

Clinical Cancer Research

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Purpose Here we assess whether molecular subtyping identifies biological features of tumors that correlate with survival and surgical outcomes of high-grade serous ovarian cancer (HGSOC). Experimental Design Consensus clustering of pooled mRNA expression data from over 2,000 HGSOC cases was used to define molecular subtypes of HGSOCs. This de novo classification scheme was then applied to 381 Mayo Clinic HGSOC patients with detailed survival and surgical outcome information. Results Five molecular subtypes of HGSOC were identified. In the pooled dataset, three subtypes were largely concordant with prior studies describing proliferative, mesenchymal, and immunoreactive tumors (concordance > 70%), and the group of tumors previously described as differentiated type was segregated into two new types, one of which (anti-mesenchymal) had down-regulation of genes that were typically upregulated in the mesenchymal subtype. Molecular subtypes were significantly associated with overall survival (p<0.001) and with rate of optimal surgical debulking (≤1 cm, p=1.9E-4) in the pooled dataset. Among stage III-C or IV Mayo Clinic patients, molecular subtypes were also significantly associated with overall survival (p=0.001), as well as rate of complete surgical debulking (no residual disease; 16% in mesenchymal tumors comparing to >28% in other subtypes; p=0.02). Conclusions HGSOC tumors may be categorized into five molecular subtypes that associate with overall survival and the extent of residual disease following debulking surgery. Because mesenchymal tumors may have features that were associated with less favorable surgical outcome, molecular subtyping may have future utility in guiding neoadjuvant treatment decisions for women with HGSOC.

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“…In this context, it is interesting an intergenic single nucleotide polymorphism (rs3753348) located between TNFRSF4 (encoding OX40) and TNFRSF18 (encoding GITR), which was associated with a 3.41-fold increased risk of death in patients with mucinous cancer [85]. The same single nucleotide polymorphism resulted predictive for the prognosis of Hashimoto's disease (HD) patients.…”

Section: Gitr May Be More Useful Than Cd25 As a Marker Of Human Tregsmentioning

confidence: 99%

“…In fact, the CC genotype was significantly more frequent in patients with mild Hashimoto's disease (HD) than in those with severe HD [P = 0.0117, odds ratio (OR) = 3.13] and correlates with a higher percentage of GITR + cells in Treg and effector T cells of patients [86]. Two more GITR-related single nucleotide polymorphisms (rs3781699 and rs9729550) are associated with increased risk of death in patients with mucinous cancer and increased risk of meningioma [85,87].…”

Section: Gitr May Be More Useful Than Cd25 As a Marker Of Human Tregsmentioning

confidence: 99%