Building a greater understanding of cancer immunology

Discovering and manipulating molecular and cellular factors dictating the quality and quantity of anti-cancer immunity to improve patient outcomes

The immune system can both promote and protect against cancer development. Determining how the immune system is subverted to drive tumour development has the potential to lead to new methods to prevent cancer development and spread, while understanding how to harness immunity for systemic, specific anti-tumour therapy presents a huge opportunity to improve outcomes for people with cancer. Both the prevention and treatment of cancer have been shown to be possible but to ensure as many patients as possible can benefit from these approaches much more knowledge is needed about the ways the immune system interacts with cancer.

Our core immunology research has three overarching aims all focused on paving the way for new therapeutic approaches to cancer including vaccines, small molecules and biological/cellular therapies, to prevent cancer where possible and to help more people live longer after a diagnosis.

Strategic programme: Immunity, cancer and metastasis

Aim 1: Understanding the role of immune cells in tumour progression and metastasis

Work from several groups at the CRUK SI highlights the importance of unconventional T cells in the initiation of cancer and in driving the metastatic cascade (Coffelt). These act, partially, through the modification of neutrophils which change their behaviour in the lung helping form the pre-metastatic niche (Coffelt, Carlin, Morton, Norman, Sansom, Steele). Following on from these fundamental observations, manipulation of neutrophil migration with small molecule inhibitors reduces metastasis in models of colorectal carcinoma and pancreatic ductal adenocarcinoma (Morton, Sansom, Steele). This has led to ongoing clinical trials seeking to improve patient outcomes (Sansom, Steele).

Building on this several groups are interrogating interactions between the tumour and the immune system to find novel ways in which the tumour subverts normal immune function to initiate, develop and spread. Ultimately these will inform future therapeutic interventions to either prevent development or to interrupt the metastatic cascade.

Aim 2: Improving T cell function within the tumour microenvironment

T cell responses against tumours are impaired right from their initiation by the immune suppressive microenvironment being transmitted to the draining lymph node (Roberts). These responses can be improved by altering the tumour microenvironment either through small molecules (Roberts) or by altering the quality of cell death within the tumour (Tait). These insights inform clinical questions about which types of treatment may induce improved T cell responses against cancer and whether these should be combined with vaccination and/or conventional therapy (Ahmad, Leung).

Understanding fundamental T cell biology also provides potential targets to improve T cell functionality within the tumour. Gene regulation within T cells has been shown to be altered within the tumour context (Cowling, Sansom). Furthermore, unconventional T cells, previously shown to be pro-tumoral, also contain anti-tumour subsets which have the potential for future therapeutic intervention (Coffelt). These data reveal potential targets to augment anti-tumour T cell responses (Cowling). Combining both an understanding of T cell intrinsic and extrinsic regulatory factors will provide further therapeutic targets to improve patient survival.

Aim 3: Defining interactions between anti-microbial responses and cancer development

The immune system is constantly changing in response to the environment. We exist surrounded by a multitude of bacteria, viruses and other potential pathogens and these all influence the set-point of our immune system. These challenges lead to alterations in later immune responses which can determine patient outcomes. At the institute we see that prior viral infection can predispose or protect against future cancer development (Roberts). The composition of the microbiome also influences tumour development within the intestine with further implications for prevention research (Maslowski).

Bacterial infection can influence tumour development and has the potential to act as a highly specific cancer therapy (Maslowski). Using immune challenges to drive anti-tumour immunity has a long history, however, with current approaches we are seeking to understand this at a mechanistic level to drive more specific, and potent, cancer therapy.

Who we are

Researchers across the institute are seeking to address these aims from those focusing entirely on cancer immunology, to those building better models of cancer to investigate specific aspects of disease in which the immune system may play a role. As such, cancer immunology is a genuinely interdisciplinary subject within the institute with everyone contributing to our progress. Labs with a core interest in cancer immunology include:

Leo Carlin – Leukocyte dynamics

Vicky Cowling – Gene regulation

Seth Coffelt – Immune cells and metastasis

Kendle Maslowski – Microbial and metabolic immune regulation

Ed Roberts – Immune priming and the tumour microenvironment

Colin Steele – Advanced colorectal carcinoma

Stephen Tait – Mitochondria and cell death