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5 results on '"Olivia Koufos"'

1. Tumour extracellular vesicles induce neutrophil extracellular traps to promote lymph node metastasis

Author

Xin Su, Ariane Brassard, Alexandra Bartolomucci, Iqraa Dhoparee‐Doomah, Qian Qiu, Thupten Tsering, Ramin Rohanizadeh, Olivia Koufos, Betty Giannias, France Bourdeau, Lixuan Feng, Julia Messina‐Pacheco, Sabrina Leo, Veena Sangwan, Daniela Quail, James Tankel, Jonathan Spicer, Julia Valdemarin Burnier, Swneke Donovan Bailey, Lorenzo Ferri, and Jonathan Cools‐Lartigue

Subjects
cancer, lymph node, metastasis, neutrophils, NETs, Cytology, QH573-671
Abstract

Abstract Lymph nodes (LNs) are frequently the first sites of metastasis. Currently, the only prognostic LN assessment is determining metastatic status. However, there is evidence suggesting that LN metastasis is facilitated by the formation of a pre‐metastatic niche induced by tumour derived extracellular vehicles (EVs). Therefore, it is important to detect and modify the LN environmental changes. Earlier work has demonstrated that neutrophil extracellular traps (NETs) can sequester and promote distant metastasis. Here, we first confirmed that LN NETs are associated with reduced patient survival. Next, we demonstrated that NETs deposition precedes LN metastasis and NETs inhibition diminishes LN metastases in animal models. Furthermore, we discovered that EVs are essential to the formation of LN NETs. Finally, we showed that lymphatic endothelial cells secrete CXCL8/2 in response to EVs inducing NETs formation and the promotion of LN metastasis. Our findings reveal the role of EV‐induced NETs in LN metastasis and provide potential immunotherapeutic vulnerabilities that may occur early in the metastatic cascade.

Published
2023
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2. Regulation of Mitochondrial Hydrogen Peroxide Availability by Protein S-glutathionylation

Author

Ryan J. Mailloux, Cathryn Grayson, and Olivia Koufos

Subjects
mitochondria, bioenergetics, glutathionylation, redox signaling, hydrogen peroxide, Cytology, QH573-671
Abstract

Background: It has been four decades since protein S-glutathionylation was proposed to serve as a regulator of cell metabolism. Since then, this redox-sensitive covalent modification has been identified as a cell-wide signaling platform required for embryonic development and regulation of many physiological functions. Scope of the Review: Mitochondria use hydrogen peroxide (H2O2) as a second messenger, but its availability must be controlled to prevent oxidative distress and promote changes in cell behavior in response to stimuli. Experimental data favor the function of protein S-glutathionylation as a feedback loop for the inhibition of mitochondrial H2O2 production. Major conclusions: The glutathione pool redox state is linked to the availability of H2O2, making glutathionylation an ideal mechanism for preventing oxidative distress whilst playing a part in desensitizing mitochondrial redox signals. General Significance: The biological significance of glutathionylation is rooted in redox status communication. The present review critically evaluates the experimental evidence supporting its role in negating mitochondrial H2O2 production for cell signaling and prevention of electrophilic stress.

Published
2022
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5. Abstract 1767: Peripheral blood neutrophil-to-lymphocyte ratio (NLR), a predictor of poor survival in cancer patients, was positively associated with the percentage of circulating low-density neutrophil fraction

Author

Ramin Rohanizadeh, Olivia Koufos, Xin Su, Ariane Brassard, Betty Giannias, France Bourdeau, Roni Rayes, Jonathan Spicer, Veena Sangwan, Swneke Bailey, Lorenzo Ferri, and Jonathan Cools-Lartigue

Subjects
Cancer Research, medicine.medical_specialty, business.industry, Cancer, Fraction (chemistry), medicine.disease, Gastroenterology, Peripheral blood, Oncology, Internal medicine, medicine, Low density, Neutrophil to lymphocyte ratio, business
Abstract

Low density (LDNs) and high density (HDNs) are two neutrophil subsets that can be separated through gradient centrifugation. LDNs was shown to be a tumor-promoting phenotype and high percentage of circulating LDNs was associated with poor cancer prognosis. In the last decade, it has also been suggested that neutrophil-to-lymphocyte ratio (NLR) is a marker of cancer-associated inflammation and high peripheral blood NLR was associated with poor cancer patient survival. Our study therefore aimed to i) establish the correlation between the percentage of circulating LDN fraction and blood NLR in cancer patients; ii) determine the differences between LDN and HDN protein expression; iii) compare the protein expression of neutrophils between cancer patients and healthy volunteers. Materials & methods: Peripheral blood of esophageal/gastric cancer patients with clinical stage of II-III were collected. Circulating LDNs and HDNs were isolated using differential density centrifugation, and protein expression determined by immunophenotyping of cells using 12 different markers. Immunophenotyping of neutrophils from healthy volunteers was compared with that of cancer patients using the same panel of markers. Results: The percentage of circulating LDN fraction varied between 0.2% to 40% in cancer patients with an average higher than that in healthy volunteers. LDN fraction was significantly elevated in patients with high peripheral blood NLR (NLR above 4). We observed a positive Pearson's correlation between NLR and LDN fraction in blood of cancer patients. Compared to HDNs, pro-tumor LDNs was bigger in size and exhibited a higher expression of Arginase 1 (Arg1), CD66b (CEACA-8), and CXCR2. Peripheral blood neutrophils (PBNs) in cancer patients, containing both HDN and LDN fractions, showed a lower expression of Arg1 and neutrophil elastase (NE). Conclusion: Higher percentage of circulating LDNs in patients with elevated blood NLR may explain the correlation between high NLR and poor survival in cancer patients. High Arg1 expression of LDNs compared to HDNs can contribute to LDNs pro-tumor activity. Decreased expression of Arg1 and NE in PBNs of cancer patients compared to healthy subjects could be due to the degranulation of PBNs in cancer patients. Citation Format: Ramin Rohanizadeh, Olivia Koufos, Xin Su, Ariane Brassard, Betty Giannias, France Bourdeau, Roni Rayes, Jonathan Spicer, Veena Sangwan, Swneke Bailey, Lorenzo Ferri, Jonathan Cools-Lartigue. Peripheral blood neutrophil-to-lymphocyte ratio (NLR), a predictor of poor survival in cancer patients, was positively associated with the percentage of circulating low-density neutrophil fraction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1767.

Published
2021

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