Intratumoral interferon regulatory factor (IRF)‐1 but not IRF‐2 is of relevance in predicting patient outcome in ovarian cancer

Zeimet, Alain G.; Reimer, Daniel; Wolf, Dominik; Fiegl, Heidi; Concin, Nicole; Wiedemair, Annemarie; Wolf, Anna Maria; Rumpold, Holger; Müller‐Holzner, Elisabeth; Marth, Christian

doi:10.1002/ijc.24214

Cited by 30 publications

(24 citation statements)

References 23 publications

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“…5b). This is in agreement with previous studies which associated a high protein expression of several IFN signaling components with a favorable clinical outcome, including IRF1 [41]. Furthermore, IFNγ inclusion in the first-line therapy of ovarian cancer resulted in an effector immune cell response [35] and a prolongation of progression-free survival [36, 37], while type I IFNs had no benefit [42].…”

Section: Discussionsupporting

confidence: 90%

Interferon signaling in ascites-associated macrophages is linked to a favorable clinical outcome in a subgroup of ovarian carcinoma patients

et al. 2017

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BackgroundAlthough tumor-associated macrophages (TAMs) are essential for cancer progression, connections between different clinical outcomes and transcriptional networks have not been reported. We have addressed this issue by analyzing global expression patterns of TAMs isolated from the ascites of ovarian cancer patients.ResultsTAMs isolated from different ovarian cancer patients can be stratified by coexpression or principal component analysis into subgroups with specific biological features and associated with distinct clinical outcomes. A hallmark of subgroup A is a high expression of clinically unfavorable markers, including (i) high CD163 expression, a surface receptor characteristic of an anti-inflammatory activation state, (ii) increased PCOLCE2 expression, indicative of enhanced extracellular matrix organization, and (iii) elevated ascites levels of IL-6 and IL-10, linked to the aggressiveness of ovarian cancer and immune suppression. In contrast, subgroup B TAMs are characterized by the upregulation of genes linked to immune defense mechanisms and interferon (IFN) signaling. Intriguingly, analysis of published data for 1763 ovarian cancer patients revealed a strong association of this transcriptional signature with a longer overall survival. Consistent with these results, IFNγ was able to abrogate the suppressive effect of ovarian cancer ascites on the inducibility of IL12B expression and IL-12 secretion, a key determinant of a cytotoxic immune response.ConclusionsThe survival of ovarian cancer patients is linked to the presence of TAMs with a transcriptional signature that is characterized by a low expression of protumorigenic and immunosuppressive markers and an upregulation of genes linked to interferon signaling. The observed IFNγ-mediated restoration of the inducibility of IL-12 in the presence of ascites provides a possible explanation for the association of an interferon signaling-associated signature with a favorable clinical outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3630-9) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

Interferon signaling in ascites-associated macrophages is linked to a favorable clinical outcome in a subgroup of ovarian carcinoma patients

et al. 2017

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“…Moreover, IRF-2 has been found to modulate the growth of pancreatic cancer cells by regulating proliferation and apoptosis effectors, such as cyclin D1 and BAX [15]. However, high expression of IRF-2 in ovarian cancer patients was reported to be associated with improved disease-free and overall survival [26]. These conflicting findings led us to investigate IRF-2 expression in human CRC tissues and its impact on patient survival.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of IRF-2 expression in colorectal cancer

et al. 2017

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Interferon regulatory factor 2 (IRF-2) is known to play a pivotal role in the development and progression of several malignancies. As a crucial member of interferon regulatory factor family, the association between the expression of IRF-2 and clinical prognostic significance has not been fully explored in colorectal cancer (CRC). The purpose of our study was to investigate the expression profile of IRF-2 in CRC and to examine its association with clinical features. The expression levels of IRF-2 in 18 paired CRC and non-cancerous colorectal tissues were measured by quantitative real-time PCR (qRT-PCR) and those in 4 paired samples by Western blotting. The results showed a significant increase in IRF-2 mRNA expression and protein expression in CRC tissues compared to those in paired normal tissues. Besides, high expression of IRF-2 was significantly associated with distant metastasis (P = 0.041) and preoperative serum CEA level (P = 0.045). Kaplan–Meier survival analysis showed that patients with high expression of IRF-2 had a significantly worse overall survival than those with low expression of IRF-2 (P = 0.006). Further multivariate analysis indicated that IRF-2 and TNM stage were independent prognostic factors for overall survival in patients with CRC. Our study primarily suggests IRF-2 as a potential prognostic biomarker in CRC.

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“…This transcriptional regulator activates specific interferons required for RNA induction as well as transcriptional activation. Interferon regulatory factor 1 is known to regulate internal levels of interferon-g and, when up-regulated, correlates with a positive prognosis in cancer patients [45]. Interferon regulatory factor 1 was down-regulated in the animals from the radioactive site receiving LPS.…”

Section: Discussionmentioning

confidence: 95%

The effects of environmental low‐dose irradiation on tolerance to chemotherapeutic agents

Howell

Gaschak

Griffith

et al. 2011

Enviro Toxic and Chemistry

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The nuclear disaster at Chernobyl, Ukraine, in April of 1986 continues to impact the environment on many different levels. Studies of epidemiological, environmental, and genetic impacts have been prolific since the accident, revealing interesting results concerning the effects of radiation. The long-tailed field mouse, Apodemus flavicollis, was collected from distinct localities near the Chernobyl site and evaluated based on in vivo responses to the current clinically employed chemotherapeutic agents bleomycin (BLM) and vinblastine (VBL), as well as the immune modulator lipopolysaccharide (LPS). Maximum tolerable doses of three different cancer drugs were administered to the rodents from three different lifestyles: native mice living and reproducing in a radioactive environment, native mice living and reproducing in an uncontaminated region, and laboratory-reared mice (Mus musculus BALB/c) with a known sensitivity to the chemical agents tested. The endpoints employed include micronucleus formation, immune cell induction, differential gene expression, and chemotherapeutic side effects such as lethargy and weight loss. In accordance with the well-studied phenomenon termed radio-adaptation, we observed varied tolerance to chemotherapeutic treatment dependent on history of ionizing radiation exposure. The results of the present study demonstrate a differential response to chemotherapeutic treatment with respect to previous levels of radiation exposure, suggesting a potential benefit associated with low-dose radiation exposure. Data reported herein could have a profound impact on the development of novel cancer treatments involving low-dose ionizing radiation.

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Intratumoral interferon regulatory factor (IRF)‐1 but not IRF‐2 is of relevance in predicting patient outcome in ovarian cancer

Cited by 30 publications

References 23 publications

Interferon signaling in ascites-associated macrophages is linked to a favorable clinical outcome in a subgroup of ovarian carcinoma patients

Interferon signaling in ascites-associated macrophages is linked to a favorable clinical outcome in a subgroup of ovarian carcinoma patients

Prognostic value of IRF-2 expression in colorectal cancer

The effects of environmental low‐dose irradiation on tolerance to chemotherapeutic agents

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