Regulation of immune responses in cancer

A hallmark of cancer is the ability of tumour cells to avoid destruction by the immune system. In some cases immune cells cannot distinguish between healthy tissue and cancerous cells, therefore they “ignore” tumours. Furthermore, while immune cells may be present within tumours, their function is frequently suppressed.

Rationale

One such mechanism is that cancer cells produce a hostile environment characterised by low levels of nutrients and high levels of immune-suppressive factors. We hypothesise that, through investigating the regulation of immune responses in cancer, we can identify new approaches to aid the development of effective treatments to help patients’ immune systems fight cancer (immunotherapies). 

Plan of work and impact of our studies

We propose to investigate two facets of immune cell activation: cell metabolism, and cell activation and signalling. We will breed mice that have modifications in genes that regulate immune cell function, metabolism, activation or in specific immune receptors This will enable us to address our hypotheses and investigate targets generally considered to improve immune cell anti-cancer function. We will use transplanted tumour cells in mice to:

  • investigate the effects of cancer cell products and nutrient availability on immune cells;
  • assess how we can manipulate metabolic or other important biochemical processes in immune cells to improve their capacity to thrive and function in tumours.

Therapies that harness the capacity of the immune system to recognise and destroy malignant cells have provided substantial benefits to cancer patients. Through our work, we hope to reveal novel aspects of immune regulation in cancer and to identify genes and mechanisms in immune and cancer cells that can be targeted to improve the efficacy of cancer immunotherapies. 

Animal Welfare and the Three Rs

Replacement 

We will study the ability of genetically modified immune cells to clear tumours in mice following injection and determine how combinations of immunotherapies can be used most beneficially. We will address key questions regarding the roles of nutrients in the tumour by manipulating their availability through dietary modification or injection of nutrients.

Reduction

The  severity classifications are mild  and moderate and we anticipate that less than 20% of mice under moderate severity protocols will experience moderate suffering as a result of tumour growth or a combination of interventions. 

Refinement

In all cases, strict monitoring regimes and humane endpoints are in place to minimise the duration and severity of any harms caused to mice through experimental protocols.   

Non-technical summary

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