Organoid modelling of the tumour immune microenvironment
SummaryColon cancer is the second most common cause of cancer death in the UK. While the early stages of the disease can be treated successfully, the prognosis for patients diagnosed with advanced disease is poor. Little progress has been made in finding the factors that mediate disease progression and in the treatment of advanced colon cancer.
New approaches to this dilemma originate from the field of tissue engineering. Here tissues are deconstructed into their individual components and systematically investigated for their function and contribution to tissue and cell growth. In a multi-disciplinary approach combining tissue engineering and tumour biology, we aim decipher the effect of the tumour’s surrounding niche on the growth of cancer cells. We aim to build a new model that includes components of the tumour’s niche and tumour tissues. We will study the role of immune cells in supporting the survival and responses of cancer cells to treatment. Since tumours behave like organs, we will grow small groups of human cells as organoids, which will allow the testing of novel therapeutics.
Therefore, we will establish a new collaboration across three different disciplines (tissue engineering, tumour biology, immunology) and institutions (QMUL, HWU, NUI Galway). Our aim is to build a tissue-engineered platform for organoid cultures (Loessner group, QMUL) using 3D bioprinting (Leslie group, HWU) to grow colon cancer cells together with fibroblasts and different types of immune cells (Ryan group, NUI Galway). A researcher from the Ryan group will be hosted in the Loessner group in London and in the Leslie group in Edinburgh to learn new techniques, including organoid cultures and 3D bioprinting. We will be using QMUL’s CREATE biofabrication lab to initiate a new in vitro model research activity. The Loessner team is involved in the public and patient information research advisory group. We will present our proposal to cancer patients and seek their feedback on our research.
Key OutputsStromal Cells Promote Matrix Deposition, Remodelling and an Immunosuppressive Tumour Microenvironment in a 3D Model of Colon, Cancers, 2021, Leonard, N, et al
Niamh Leonard developed a viable 3D colorectal cancer model for possible use in the study of disease and therapeutics.
A 3D colon cancer model to study the role of mesenchymal stromal cells in cancer growth and immune suppression OOAC e-Symposium April 2021, abstract presentation, Niamh Leonard