Chemotherapy & immunotherapy for metastatic ovarian cancer

Chemotherapy & immunotherapy for metastatic ovarian cancer

Prof Balkwill's team in Clinical Cancer Research: chemotherapy pre-surgery could boost immunotherapy's power

Closing the proton gate

Closing the proton gate

New options for leukaemia treatment from the Capasso lab, targeting the flow of protons across B Cells

CanBuild: Royal Society Summer Science Exhibition 2016

CanBuild: Royal Society Summer Science Exhibition 2016

Visit the exhibition to find out more about our exciting 3D tumour engineering project

Centre for Cancer & Inflammation

Our centre focuses on the links between cancer and inflammation. The overarching hypothesis that drives our research is that the inflammatory mediators and cells found in cancer are more likely to enhance than inhibit tumour progression; hence modulating these cells and mediators should be of therapeutic benefit.

Our aim is to translate our laboratory research in chronic inflammation and the tumour microenvironment into new treatments for cancer, especially ovarian and pancreatic cancer. We have been involved in several Phase I and Phase II clinical trials of cytokine antagonists and are currently planning other trials involving novel targets in the cancer microenvironment.

We also have a strong commitment to public engagement via the University's Centre of the Cell, an innovative and successful science centre and science outreach project for young people.

Group Leaders in the Centre

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Life in the Centre

Get a sense of what life is like for researchers in the Centre:

Results & Discoveries

Time-lapse experiment of a live ex vivo human High Grade Serous Ovarian Cancer omentum metastatic tumour slice, stained with CD11b (red), EpCAM (green) and fibronectin (pink). Images are maximum intensity projections of 8 z slices, acquired every 30 seconds for 30 minutes. The fibronectin staining shows the extracellular matrix, CD11b shows tumour-associated macrophages (TAMs) and EpCAM shows tumour cells. This video highlights TAMs' movements within a live human tumour microenvironment.

Our recent discoveries and results include:

  • The first profile of an evolving human metastatic microenvironment, measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, ECM organization and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer (HGSOC) metastases that ranged from minimal to extensive disease, we show how non-malignant cell densities and cytokine networks evolve with disease progression (1).
  • Defining the effects of neoadjuvant chemotherapy on the host immune system in biopsies from ovarian cancer patients (2,3).
  • Discovering a pattern of expression of 22 matrisome genes in tumour biopsies that distinguishes patients with a shorter overall survival in ovarian and twelve other primary solid cancers, suggesting that there may be a common matrix response to human cancer (1).
  • Defining the mechanisms of action of inhibiting the chemokine receptor CCR4 in the tumour microenvironment (4).
Selected recent publications:

(1) Pearce OMT*, Delaine-Smith R.*, Maniati, E.*, et al Deconstruction of a metastatic tumor microenvironment reveals a common matrix response in human cancers Cancer Discovery (2017) DOI: 10.1158/2159-8290.CD-17-0284 * equal contribution

(2) Montfort A, Pearce O, Maniati E, Vincent BG, Bixby L, Böhm S, Dowe T, Wilkes EH, Chakravarty P, Thompson R, Topping J, Cutillas PR, Lockley M, Serody JS, Capasso M, Balkwill FR. A strong B-cell response is part of the immune landscape in human high-grade serous ovarian metastases. Clinical Cancer Research (2016) 23 250-262

(3) Böhm S, Montfort A, Pearce OMT, Topping J, Chakravarty P, Everitt GLA, Clear A, McDermott JR, Ennis D, Dowe T, Fitzpatrick A, Brockbank EC, Lawrence AC, Jeyarajah A, Faruqi AZ, McNeish IA, Singh N, Lockley M, Balkwill FR. Neoadjuvant chemotherapy modulates the immune microenvironment in metastases of tubo-ovarian high-grade serous carcinoma. Clinical Cancer Research (2016) 22 3025-36

(4) Berlato C, Khan MN, Schioppa T, Thompson R, Maniati E, Montfort A, Jangani M, Canosa M, Kulbe H, Hagemann UB, Duncan A, Fletcher L, Wilkinson RW, Powles T, Quezada S, Balkwill FR. A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer. J Clin Invest (2017) 127 801-813

CanBuild

The European Research Council (ERC) has awarded Professor Fran Balkwill's team a €2.43million grant for a project that aims to revolutionise the field of cancer cell research: using bioengineering techniques to grow the first complex 3D human tumour in the laboratory.

News and links to further information about the project:

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