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Jacqui Shields

Dr Jacqui Shields

Biography | Pubmed

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Stroma Function in the Tumour Microenvironment

Current immunotherapy approaches show great promise but are effective in just a few cancer types. Therefore, a clear knowledge deficit exists in our understanding of anti-tumour immunity and the suppressive networks at play during the different stages of malignant transition.

Surveillance by the immune system has been implicated as a major barrier to the progression of early cancers, however, tumours have developed strategies to interfere with almost every step necessary for an effective anti-tumour immune response. "Normal” cells termed the stroma in surrounding tissue - including fibroblasts, endothelial cells, pericytes and immune cells - form a tumour microenvironment that co-evolves with cancer from its earliest stages to shape progression, and mounting evidence indicates that components of the stroma support immune suppression to promote carcinogenesis via mechanisms that remain poorly understood.

By integrating experimental cancer models, complex in vitro systems and high throughput genomics to understand how the tumour stroma regulates immune activity from early stages of disease to promote carcinogenesis the Shields Lab aims to address the following key questions: 

 

 

How do stromal cells respond to cancer-derived signals to shape the microenvironment and support carcinogenesis?

Identifying the mechanisms of stromal-mediated immune dysfunction from the earliest step of tumour development to reveal how an initially protective role switches to propagate disease.

 

 

How do lymph nodes contribute to loss of immune control during carcinogenesis?

With an focus on stroma-immune crosstalk, we aim determine how draining lymph nodes respond to early cancer-derived signals

 

 

 

 

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Can we exploit the stroma for clinical application?

Our longer-term goal is to translate our findings that different stromal populations modulate distinct responses at different stages of disease for patient benefit; from patient stratification to early intervention

Contact:

Click here to contact Dr Jacqui Shields by email.

 

Recent Publications:

Sarah Davidson, Mirjana Efremova, Angela Riedel, Bidesh Mahata, Roser Vento-Tormo, Jhuma Pramanik, Gozde Kar, Jani Huuhtanen, Jacqueline D. Shields*, Sarah A. Teichmann* (2020). Single cell RNA sequencing reveals a dynamic stromal niche within the evolving tumour microenvironment. Cell Reports. In Press.

Munir, H; Jones, JO; Janowitz, T; Martins, CP; Welsh SJ; Shields J (2020). Stromal Amyloid β drives Neutrophil extracellular trap formation to augment tumour growth. bioRxiv. doi:10.1101/2020.01.10.901686

Mahata, B. P., J.; Van der Weyden. L.;  Kar, G.; Riedel, A.; Ryder, E.; Duddy, G.; Adams, DJ.; Shields, JD*.; Teichmann. SA* (2019). Tumors induce de novo steroid biosynthesis in T cells to evade immunity. bioRxiv. doi:https://doi.org/10.1101/2020.01.10.901686

Pedro L, Harmer Q, Mayes E, Shields JD (2019). Impact of Locally Administered Carboxydextran-Coated Super-Paramagnetic Iron Nanoparticles on Cellular Immune Function. Small. 15 (20) 1900224.

Ricardo Miragaia, Tomás Gomes, Agnieszka Chomka, Laura Jardine, Angela Riedel, Ahmed N Hegazy, Ida Lindeman, Guy Emerton, Thomas Krausgruber, Jacqueline Shields, Muzlifah Haniffa, Fiona Powrie, Sarah A Teichmann (2019). Single cell transcriptomics of regulatory T cells reveals trajectories of tissue adaptation. 5 Feb. Immunity. 50 (2) 493-504.

 David Shorthouse, Angela Riedel, Emma Kerr, Luisa Pedro, Dora Bihary, Shamith Samarajiwa, Carla Martins, Jacqueline Shields*, Benjamin A Hall* (2018). Role of stromal osmoregulation in cellular transformation in cancer and disease. Nature Communications. 9(1):3011.

Tamara Muliaditan, Mary Okesola, Jonathan Caron, Mirella Georgouli, Peter Gordon, Sharanpreet Lall, Desislava Kuzeva, Luisa Pedro, Jacqueline D. Shields, Cheryl E. Gillett, Sandra S. Diebold, Victoria Sanz-Moreno, Tony Ng, Esther Hoste, and James N. Arnold (2018). Tumour-associated macrophages exploit an innate wound healing response to facilitate metastasis. Nature Communications. 9(1):2951.

M Lakins, E Ghorani, H Munir, C Martins, JD Shields (2018). Cancer-associated Fibroblasts Provide Immune Protection to Tumor Cells via Antigen-Specific Deletion of CD8+ Cytotoxic T Cells. Nature Communications.. 9: 948.  

A Riedel, D Shorthouse, BA Hall, JD Shields (2016). Tumor induced stromal reprogramming drives lymph node transformation. Nature Immunology. 17(9): 1118–1127.

* Co-corresponding Author

·         dentifying the mechanisms of stromal-mediated immune dysfunction from the earliest step of tumour development to reveal how an initially protective role switches to propagate disease.