Tumours are not only made of tumour cells. Instead, tumours, especially solid tumours, such as pancreatic, colorectal, liver and breast tumours, are surrounded by non-cancerous cells that include immune cells and fibroblasts and form what is known as the tumour stroma. The tumour stroma can represent up to 90% of the tumour mass and immune cells and fibroblasts can either inhibit or support tumour progression.
However, the mechanisms by which immune cells and fibroblasts interact with tumour cells to support cancer progression are not completely understood.
Both the Schmid Lab and the Mielgo Lab, have joined forces to investigate this important question using a variety of pre-clinical physiologically relevant models that mimic the complexity of the tumour microenvironment and a combination of state of the art technologies they have established, including: single cell RNA sequencing, proteomics, flow/mass cytometry and spatial transcriptomics.
Our overall goal is to understand the complex interactions between tumour cells, immune cells and fibroblasts in order to identify new combination treatments that target both the tumour cells and the tumour supporting functions of the tumour stroma.
Two major challenges in cancer are: resistance to therapies and metastasis (spreading of tumour cells to other organs).
Funded by CRUK, the Royal Society, MRC and North West Cancer Research, the Schmid Lab is led by Professor Michael Schmid, who is Head of the Department of Molecular and Clinical Cancer Medicine. His lab is looking at how non-cancerous stroma cells promote the spread of tumour cells from the primary tumour site to other distant organs. Michael's lab has recently revealed that a sub-group of myeloid immune cells promote the metastatic process of cancers to the liver. Myeloid cells accumulate in large numbers at the metastatic site in the liver and these myeloid cells secrete factors and provide molecular signals that help disseminated cancer cells to grow and form deadly metastatic tumours.
"One of our interests is to understand how myeloid immune cells modulate liver metastases and the response of metastatic liver tumours to cytotoxic and immuno-therapies," Professor Schmid explains. "Applying a transdisciplinary approach by combining different research areas and new technologies, including single cell transcriptomics, mass cytometry, pre-clinical mouse models and patient explant models allows us to identify new therapeutic molecular targets to improve current diagnostics and treatment options for cancer patients with liver metastases".
Funded by the Wellcome Trust, the Royal Society and North West Cancer Research, the Mielgolab is led by Dr Ainhoa Mielgo, who is the Programme Director of the Cancer Biology and Therapy MSc - University of Liverpool and investigates how tumour cells interact with the surrounding immune cells and fibroblasts and how these interactions affect cancer progression, response to therapies and the immune response against cancer. “Our overall goal is to find effective combination treatments that target both the cancer cells and the tumour promoting functions (while at the same time sparing the anti-tumorigenic functions) of the non-malignant surrounding cells,” says Dr Mielgo. “Finding which signalling networks are activated within the tumour microenvironment and identifying those that support cancer progression could lead to the development of more effective treatments.”
Back to: Liverpool Cancer Research Institute