A5045047956- Cancer Immunotherapy and Biomarkers
- Cancer, Stress, Anesthesia, and Immune Response
- Biosimilars and Bioanalytical Methods
- Immune cells in cancer
- Tryptophan and brain disorders
- Inflammatory Biomarkers in Disease Prognosis
- Inflammatory mediators and NSAID effects
- Cancer-related Molecular Pathways
- Computational Drug Discovery Methods
- Estrogen and related hormone effects
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Immune Cell Function and Interaction
Medicines Discovery Catapult
2024
Cancer Research UK Manchester Institute
2020-2022
University of Manchester
2020-2022
Inflammation can support or restrain cancer progression and the response to therapy. Here, we searched for primary regulators of cancer-inhibitory inflammation through deep profiling inflammatory tumor microenvironments (TMEs) linked immune-dependent control in mice. We found that early intratumoral accumulation interferon gamma (IFN-γ)-producing natural killer (NK) cells induced a profound remodeling TME unleashed cytotoxic T cell (CTL)-mediated eradication. Mechanistically, tumor-derived...
Identifying strategies to improve the efficacy of immune checkpoint blockade (ICB) remains a major clinical need. Here, we show that therapeutically targeting COX2/PGE2/EP2-4 pathway with widely used nonsteroidal and steroidal anti-inflammatory drugs synergized ICB in mouse cancer models. We exploited bilateral surgery model distinguish responders from nonresponders shortly after treatment identified acute IFNγ-driven transcriptional remodeling responder mice, which was also associated...
Abstract Cytotoxic therapies, besides directly inducing cancer cell death, can stimulate immune-dependent tumor growth control or paradoxically accelerate progression. The underlying mechanisms dictating these opposing outcomes are poorly defined. Here, we show that cytotoxic therapy acutely upregulates cyclooxygenase (COX)-2 expression and prostaglandin E 2 (PGE ) production in cells with pre-existing COX-2 activity. Screening a compound library of 1280 approved drugs, find all classes...
Abstract Introduction Radiotherapy is a key treatment for various cancers, with nearly 50% of all cancer patients receiving it as part their therapeutic plan. It can activate cytotoxic signaling pathways to promote cell death but also trigger cytoprotective mechanisms that respond cellular damage. These be inhibited by targeted anticancer agents such DNA damage response (DDR) agents, suggesting radiotherapy could enhance the efficacy these drugs. This study presents data showing enhances...
<div>Abstract<p>Identifying strategies to improve the efficacy of immune checkpoint blockade (ICB) remains a major clinical need. Here, we show that therapeutically targeting COX2/PGE<sub>2</sub>/EP2-4 pathway with widely used nonsteroidal and steroidal anti-inflammatory drugs synergized ICB in mouse cancer models. We exploited bilateral surgery model distinguish responders from nonresponders shortly after treatment identified acute IFNγ-driven transcriptional...
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<p>Supplementary Figures and supplementary Methods</p>
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<p>Table S5</p>
<p>Table S1</p>
<p>Table S7</p>
<p>Table S6</p>
<p>Table S3</p>
<p>Table S1</p>
<p>Supplementary Figures and supplementary Methods</p>
<p>Table S2</p>
<p>Table S4</p>
<p>Table S5</p>
<div>Abstract<p>Identifying strategies to improve the efficacy of immune checkpoint blockade (ICB) remains a major clinical need. Here, we show that therapeutically targeting COX2/PGE<sub>2</sub>/EP2-4 pathway with widely used nonsteroidal and steroidal anti-inflammatory drugs synergized ICB in mouse cancer models. We exploited bilateral surgery model distinguish responders from nonresponders shortly after treatment identified acute IFNγ-driven transcriptional...