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Scott Keith
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Scott Keith

AS SEEN ON
Cancer Research Prevention

Geo Focus

United States (National)

Coverage Attributes:

Beta
Data Driven: 50 %
Informative: 50 %

Themes Covered:

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Pitching Insights

Scott Keith's coverage focuses on local news and events in St. Helens, with a particular emphasis on city management, community events, economic development, and transportation. Given this focus, Scott would likely be most receptive to pitches related to upcoming local events or developments within the St. Helens area.

Sources who can provide insights into local government decisions or initiatives related to city management, economic development projects, or transportation improvements in the St. Helens region are likely to resonate well with his coverage interests.

Given that a significant portion of his coverage includes press releases and government announcements, public relations professionals representing relevant organizations should consider reaching out when they have newsworthy updates aligned with Scott's areas of interest.

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Articles

Cancer Research Prevention

Extracellular matrix-myCAF signatures correlate with resistance to neoadjuvant aPD-L1 immune checkpoint inhibition with durvalumab + metformin in HPV+ HNSCC

By: Pablo Llerena, Hani Samarah, Kathryn Nunes, Kelly Bridgham, Sruti Tekumalla, Amiti Jain, Larry Harshyne, Sanket K. Shukla, Ioannis Vathiotis, Madalina Tuluc, Stacey Gargano, John R. Eisenbrey, Scott Keith, David M. Cognetti, Adam J. Luginbuhl, Rita Axelro

Background: Immune checkpoint inhibitors (ICI) have demonstrated clinical benefit in head and neck squamous cell carcinoma (HNSCC); however, single-agent efficacy is limited, leaving significant unmet needs. Metformin may synergize with ICI, offering promise to improve response rates. We leveraged multi-omic data from a randomized, presurgical neoadjuvant trial (NCT03618654) evaluating a single infusion of the anti-programmed death ligand 1 (PD-L1) ICI, durvalumab, with or without daily, standard dose metformin in previously untreated, non-diabetic patients with HNSCC to understand predictors of response and the effect of combination therapy. Methods: Clinical, pathological, and correlative data were analyzed to investigate response and resistance mechanisms. We present an in-depth multi-omic analysis of primary tumor specimens to study treatment response/resistance in HPV+ HNSCC. Results: Baseline samples revealed that myofibroblastic cancer-associated fibroblast (MYCAF) and extracellular matrix (ECM) signatures were enriched in durvalumab plus metformin (DM) nonresponders which were localized to the leading tumor edge on spatial transcriptomics. In contrast, baseline responder samples were enriched for the Langerhans-like dendritic cell (DC) state and interferon (IFN) signatures. Treatment increased intratumoral CD8+ T cell and IFN signatures and peripheral blood CCL2 levels. Responders demonstrated macrophage and dendritic cell enrichment and antigen processing and presentation upregulation. Enrichment of cell cycle-related gene sets, specifically the MYC targets V1 Hallmark gene set, correlated with nonresponse. Conclusion: Early response and resistance dynamics for DM in HPV+ HNSCC reveal baseline ECM-MYCAF as predictive of nonresponse. In contrast, responders were distinguished by baseline enrichment in the Langerhans-like DC cell state and post-treatment antigen-presenting gene sets.

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