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Your search keyword '"Hayley Simon"' showing total 6 results
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6 results on '"Hayley Simon"'

1. JAML immunotherapy targets recently activated tumor-infiltrating CD8+ T cells

Author

Simon Eschweiler, Alice Wang, Ciro Ramírez-Suástegui, Adrian von Witzleben, Yingcong Li, Serena J. Chee, Hayley Simon, Monalisa Mondal, Matthew Ellis, Gareth J. Thomas, Vivek Chandra, Christian H. Ottensmeier, and Pandurangan Vijayanand

Subjects
CP: Cancer, CP: Immunology, Biology (General), QH301-705.5
Abstract

Summary: Junctional adhesion molecule-like protein (JAML) serves as a co-stimulatory molecule in γδ T cells. While it has recently been described as a cancer immunotherapy target in mice, its potential to cause toxicity, specific mode of action with regard to its cellular targets, and whether it can be targeted in humans remain unknown. Here, we show that JAML is induced by T cell receptor engagement, reveal that this induction is linked to cis-regulatory interactions between the CD3D and JAML gene loci. When compared with other immunotherapy targets plagued by low target specificity and end-organ toxicity, we find JAML to be mostly restricted to and highly expressed by tissue-resident memory CD8+ T cells in multiple cancer types. By delineating the key cellular targets and functional consequences of agonistic anti-JAML therapy in a murine melanoma model, we show its specific mode of action and the reason for its synergistic effects with anti-PD-1.

Published
2023
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2. Linkages between Adolescents' Social Networking Site Use, Quality of Friendship, Co-Rumination, and Self-Disclosure Practices

Author

Hayley Simon

Abstract

This study examined the relationship between quality of friendship and social networking site (SNS) usage, co-rumination, and self-disclosure among 355 adolescents aged 11 to 15. Participants completed an online questionnaire addressing frequency, intensity, and rate of their online communication, how they perceived the positive and negative aspects of their peer relationships; and the methods with which they discussed problems with friends. Participants were also asked to list up to 10 individuals with whom they interacted most when using SNS and face-to-face to identify overlaps in their on- and off-line friendships. Findings showed that quality of friendship was positively correlated with co-rumination and self-disclosure, and that SNS usage was positively correlated with age and overlaps in online and offline friendship. Results indicated a positive effect of age and self-disclosure on quality of friendship. A main effect of gender was found whereby girls reported higher SNS usage, and levels of co-rumination, and self-disclosure than boys. Developmental differences were examined qualitatively through participants' reports of the overlap in friendship, in which participants ages 14 to 15 showed greater overlap in their online and offline relationships when compared with participants ages 11 to 13. SNS usage served as a predictor of the level of overlap found between online and offline friendships. Collectively, these findings emphasize the importance of understanding SNS usage in adolescence, as peer relationships and internet usage continue to increase in importance with age. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Published
2024

6. Cytotoxic CD4+ tissue-resident memory T cells are associated with asthma severity

Author

Sara Herrera de la Mata, Ciro Ramírez-Suástegui, Heena Mistry, Mohammad A. Kyyaly, Hayley Simon, Shu Liang, Laurie Lau, Clair Barber, Monalisa Mondal, Syed Hasan Arshad, Ramesh J. Kurukulaaratchy, Pandurangan Vijayanand, and Grégory Seumois

Subjects
Immunology, Immunology and Allergy
Abstract

Patients with severe uncontrolled asthma represent a distinct endotype with persistent airway inflammation and remodeling that is refractory to corticosteroid treatment. To determine T cell subsets and effector molecules that drive pathogenesis of severe asthma, we performed single-cell transcriptome analysis of >50,000 airway CD4+ T cells isolated from bronchoalveolar lavage (BAL) samples from 30 patients with mild and severe asthma. We observed striking heterogeneity in the nature of CD4+ T cells present in asthmatics' airways with tissue-resident memory (TRM) cells making a dominant contribution. Notably, in severe asthmatics a subset of CD4+ TRM cells (CD103-expressing) was significantly increased, comprising nearly 65% of all CD4+ T cells in the airways of male patients with severe asthma when compared to mild asthma (13%). This subset was enriched for transcripts linked to T cell receptor (TCR) activation (HLA-DRB1, HLA-DPA1, CD40LG) and cytotoxicity (GZMB, GZMH), and following stimulation expressed high levels of transcripts encoding for pro-inflammatory non-TH2 cytokines (CCL3, CCL4, CCL5, TNF, LIGHT) that could fuel persistent airway inflammation and remodeling. Our findings indicate the need to look beyond the traditional T2 model of severe asthma to better understand the heterogeneity of this disease. This work was supported by (i) NIH research grant R01HL114093 (PV) and equipment grants (S10RR027366 - BD FACSAria Fusion, and S10OD025052 - Illumina Novaseq 6000); the William K. Bowes Jr. Foundation (P.V.). The WATCH study is supported by the Southampton NIHR Biomedical Research Centre and the Southampton NIHR Clinical Research Facility which are funded by the NIHR and are a partnership between the University of Southampton and University Hospital Southampton NHS Foundation Trust.

Published
2022
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