Pathfinder: Defining interactions between the cytokine IL-22 and oncogenic KRAS as a new therapeutic target in colorectal cancer

Lead Research Organisation: University of Oxford
Department Name: Botnar Research Centre

Abstract

Colorectal cancer is the second most common cause of cancer related death in the UK. Each year roughly 41,000 people are diagnosed with colorectal cancer. Colorectal cancers contain DNA mutations that cause the cancer cells to grow and divide uncontrollably. One of these mutations occurs in a gene called KRAS, a key controller of growth and cell division. When mutated, KRAS becomes locked in its active state and sends constant signals into a cell promoting growth and survival. 40-45% of colorectal cancer patients have KRAS mutations in their tumours. These tumours are poorly responsive to standard therapy and no therapies currently in development have shown any success in their treatment. Therefore, there is an urgent need to find new ways to treat patients with this specific type of colorectal cancer.

Our studies have provided early evidence that in some patients with KRAS mutant tumours, a molecule secreted by cells of the immune system, called interleukin 22 (IL-22), might be fueling tumour development. Interleukin 22 is a double-edged sword in the colon. Under normal circumstances, it helps to repair damage to the cells lining the colon; in tumours, however, this normally beneficial molecule can promote cancer cell growth and survival. Patients whose tumours have both high levels of the IL-22 receptor and KRAS mutations have a very poor prognosis. This is not the case in patients with KRAS mutant tumours expressing low levels of the interleukin 22 receptor. It seems that IL-22 has different effects in cells that have KRAS mutations versus those that do not. IL-22 synergizes with mutated KRAS to promote cancer progression and shorten survival. Therefore, we have identified a subgroup of patients representing approximately 50% of KRAS mutant colorectal cancers, whom we believe may benefit from therapeutic strategies designed to neutralize IL-22.

All of our data thus far has come from retrospectively assessing information on gene expression and survival in large patient cohorts. In the first phase of this study, we will try to better understand IL-22 signaling in tumours with and without KRAS mutations. We will use biopsies taken from patients at the time of diagnosis and tissue samples from their surgically resected tumours to investigate interleukin 22 signaling. The second phase of this study will investigate the effects of blocking IL-22 signaling in colorectal cancer in an early phase clinical trial. This type of trial is called a Phase 0 window trial which takes advantage of the window of time between patient diagnosis and when they have surgery for tumour removal. We will recruit defined subgroups of patients whose tumours either have high or low IL-22 receptor expression and have or do not have KRAS mutations. Patients who wish to be included in the trial will be given a single dose of an antibody that blocks either the IL-22 pathway or molecules that promote IL-22 production (e.g. a related molecule named interleukin-23). By examining the differences between the biopsies taken from these patients before the treatment and their resected tumour after the treatment, we will determine whether the treatment successfully reduced IL-22 signaling. Furthermore, we will identify patient subgroups in which IL-22 blockade is most effective. Based on our existing data, we expect that patients whose tumours express high levels of the interleukin 22 receptor and are mutant for KRAS will be most amenable to IL-22 pathway blockade.

The results of this study will pave the way to larger clinical trials using IL-22 pathway blockade in specific molecular subgroups of colorectal cancer. There are currently no effective therapeutic options for KRAS mutant colorectal cancer patients and they represent a group of unmet clinical need. However, using a novel approach of blocking an immune signal in the context of KRAS mutation, we hope to identify a viable therapeutic option for a subset of these patients.

Technical Summary

Inflammation driven by the IL-23/Th17 cell axis is related to poor outcome in colorectal cancer. Cytokines produced during Th17 responses, such as IL-22, promote CRC development in animal models by acting directly on intestinal epithelial cells to promote growth and survival.

The KRAS oncogene is mutated in roughly 45% of colorectal cancer. No targeted therapies currently in development have shown any activity in KRAS mutant CRC and finding novel approaches is a high priority. The available literature suggests that KRAS mutations have little prognostic impact, but our recent studies have shown that among tumours with evidence of heightened IL-22 signalling, KRAS mutations are strongly associated with poor clinical outcome. (McCuaig et al., submitted). Specifically, using tumour transcriptomic datasets totalling nearly 2000 patients (GSE39582, PETACC3, TCGA, ALMAC), we have identified that in patients with high tumoural expression of either or both subunits of the heterodimeric IL-22 receptor (IL22RA1, IL10RB), KRAS mutation dramatically worsens prognosis. In contrast, KRAS has no prognostic relevance in tumours with low expression of IL-22 receptor subunits. Based on this data we hypothesize that modulation of the IL-22 pathway in IL22RA1-high, KRAS mutant tumours may have therapeutic benefit.

Though attractive as a possible therapeutic target for CRC, direct evidence supporting a tumourigenic role for IL-22 in humans is lacking. Furthermore, as KRAS is widely considered an "undruggable" target, methods of improving clinical outcome for patients with KRAS-mutant CRC are urgently needed. We will address both knowledge gaps by studying the role of IL-22 signalling in KRAS wild type versus mutant CRC in order to 1) establish the functional relevance of IL-22 signalling in human CRC; and 2) test the biological impact of IL-22 or IL-23 blockade in molecularly stratified CRC patient subsets in a Phase 0 window trial.

Planned Impact

Colorectal cancer is the second most common cause of cancer related death in the UK. The KRAS oncogene is mutated in roughly 45% of colorectal cancer. No targeted therapies currently in development have shown any activity in KRAS mutant CRC and finding novel approaches is a high priority. Such patients have a major unmet clinical need. In resectable CRC, the presence of KRAS mutation carries a minor adverse prognostic impact, but our recent studies have shown that in nearly 50% of patients whose tumours carry KRAS mutation, heightened IL-22 signaling is strongly associated with poor prognosis. This proposed experimental medicine study provides the next logical step in the clinical translation of this knowledge by exploring the effects of directly modulating IL-22 signaling in newly diagnosed CRC patients.

Data from this study with benefit a range of stakeholders, most importantly KRAS mutant CRC patients (a new therapeutic strategy for which there are currently no efficacious targeted therapies, with a clear pathway to efficacy testing through FOCUS-4 in stage IV patients); clinicians and the National Health Service (NHS) (through guidelines for patient stratification and improved resource uiltisation); Pharma/Biotech companies (through commercialisation of a biomarker test for IL22R expression and repurposing of existing assets licensed for inflammatory diseases in cancer); the UK economy broadly, and researchers (through greater understanding of synergies between cytokine signaling and oncogenic drivers in CRC and other cancers).

Results of this study will provide useful knowledge regarding the effects of IL-22 in human CRC and the precise molecular subtypes in which IL-22 blockade is most efficacious. This will provide a rationale from which to design and deploy anti-IL-22 trials with efficacy endpoints. The FOCUS4-C arm of the multi-site molecularly stratified FOCUS-4 colorectal cancer trial lead by Prof Tim Maughan will recruit KRAS mutant patients and represents a clear pathway to efficacy testing of anti-IL-22 therapy in stage IV patients. The results of these studies will define new guidelines for stratification of patients with KRAS mutant CRC and allow clinicians to stratify patients to targeted therapy based not only upon a genetic signature, but the unique integration of a genetic and immune signature.

The immune system is a double edge sword in cancer with beneficial anti-tumour immunity on one side and tumour-promoting inflammation on the other. Much excitement in the clinical and pharmaceutical spheres has emerged in recent years with the success of immune checkpoint blockade in some cancers. Combinatorial therapies harnessing anti-tumour immunity are an area of ongoing basic and clinical research. However, checkpoint blockade has shown minimal efficacy in colorectal cancer and only patients with microsatellite unstable tumours show any response. Preclinical studies from our lab and others support a strong pro-tumourigenic role for Th17-derived cytokines in CRC. This study will serve as an important proof of concept around targeting pro-tumourigenic cytokine signaling in the context of certain oncogenic mutations in cancer and allow for repurposing of existing assets licensed for inflammatory diseases in cancer. Furthermore, the commercialisation of a standardised immunohistochemical/gene expression based biomarker assay for measurement and patient stratification based on IL22R expression will foster academic/industrial partnerships leading to IP generation and wider economic benefit to the UK.

Finally, the novel synergy between cytokine signaling and an oncogenic driver is not unique to colorectal cancer. The biological understanding gleaned from this work will provide a launching point for further translational research for KRAS-IL-22 synergies in other cancers (ie. pancreatic cancer where KRAS mutation prevalence is 95%) and to explore other cytokine synergies with other oncogenic drivers.

Publications

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Mann EH (2020) Fusobacterium nucleatum, rectal cancer and radiotherapy. in Annals of oncology : official journal of the European Society for Medical Oncology

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McCuaig S (2020) The Interleukin 22 Pathway Interacts with Mutant KRAS to Promote Poor Prognosis in Colon Cancer. in Clinical cancer research : an official journal of the American Association for Cancer Research

 
Description Clinical Research Training Fellowship
Amount £193,323 (GBP)
Funding ID C2195/A28699 
Organisation Cancer Research UK 
Department Cancer Research UK (CRUK) Oxford Centre
Sector Private
Country United Kingdom
Start 10/2019 
End 09/2023
 
Description Kennedy Trust Prize Studentship
Amount £111,313 (GBP)
Organisation The Kennedy Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2017 
End 10/2021
 
Title Organoid co-cultures (immune and microbiota) 
Description Organoids are self-organising 3D culture systems of epithelial tissue that allow the stable culture of patient-derived tumours and matched normal lines in vitro. They can be used to test how tumours respond to different stimuli including metabolites and cytokines both alone. To date, poor accessibility to the enclosed apical surface makes culture with microbiota components challenging (Co, Margalef-Catala et al. 2019). However, alongside collabortors we are developing expertise in Oxford to perform intra-organoid microinjections of bacteria (Dutta and Clevers 2017) and reverse the polarity of the epithelial cells so that microbial species can be added directly in the media (Co, Margalef-Catala et al. 2019). We are now working to co-culture these microbe-treated organoids with immune and mesenchymal cells to study the effect in a relatively reductionist approach on the cells of the tumour microenvironment. 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2020 
Provided To Others? No  
Impact Robust optimisation of organoid-microbiome-immune co-cultures will allow for rapid screening of candidate microbes and drugs, enabling researchers to untangle the connections between these cells types which may be therapeutically tangible. 
 
Description CRUK Grand Challenge - Manipulating the microbiome to beat cancer 
Organisation Dana-Farber Cancer Institute
Country United States 
Sector Hospitals 
PI Contribution My lab is part of the OPTIMISICC consortium that brings together 14 investigators from Canada, The Netherlands, Spain, USA and UK with expertise in genomics, microbiology, genetics, immunology, epidemiology and pathology. The goal is to discover how certain microbes inside the body contribute to cancer development and treatment responsiveness and to harness this knowledge for novel therapeutic approaches. My lab is contributing to experimental characterisation of the interactions between the host and microbiome in driving colorectal cancer, with a focus on the immune response. This includes the identification of bacterial species and functions that promote metastatic colorectal cancer in mouse models, and examining the concurrent key host pathways involved in immune and tissue responses. We will also re-create the complex tumour microenvironment by probing co-culture of immune and stromal cells with patient-derived organoids in the presence or absence of specific microbes and/or metabolite cocktails.
Collaborator Contribution Partners across the collaboration are comparing the gut microbiome from thousands of people at risk of developing bowel cancer to look for associations between the microbiome and cancer development. These studies will also examine the epidemiology of bowel cancer and microbiome characteristics, as well as the localisation of bacteria within the tumour. The research aims to develop, test and implement microbiome-targeted therapeutic approaches for colorectal cancer through analysis of cancer models, pre-clinical development and clinical trials of novel therapeutics. These studies will accelerate understanding of how the microbiome can be used to diagnose, stratify patients and treat cancer.
Impact No outputs to date. This is a multidisciplinary collaboration bringing together cancer biology, clinical trials, cancer modelling and immunology.
Start Year 2019
 
Description CRUK Grand Challenge - Manipulating the microbiome to beat cancer 
Organisation Harvard University
Department Harvard Medical School
Country United States 
Sector Academic/University 
PI Contribution My lab is part of the OPTIMISICC consortium that brings together 14 investigators from Canada, The Netherlands, Spain, USA and UK with expertise in genomics, microbiology, genetics, immunology, epidemiology and pathology. The goal is to discover how certain microbes inside the body contribute to cancer development and treatment responsiveness and to harness this knowledge for novel therapeutic approaches. My lab is contributing to experimental characterisation of the interactions between the host and microbiome in driving colorectal cancer, with a focus on the immune response. This includes the identification of bacterial species and functions that promote metastatic colorectal cancer in mouse models, and examining the concurrent key host pathways involved in immune and tissue responses. We will also re-create the complex tumour microenvironment by probing co-culture of immune and stromal cells with patient-derived organoids in the presence or absence of specific microbes and/or metabolite cocktails.
Collaborator Contribution Partners across the collaboration are comparing the gut microbiome from thousands of people at risk of developing bowel cancer to look for associations between the microbiome and cancer development. These studies will also examine the epidemiology of bowel cancer and microbiome characteristics, as well as the localisation of bacteria within the tumour. The research aims to develop, test and implement microbiome-targeted therapeutic approaches for colorectal cancer through analysis of cancer models, pre-clinical development and clinical trials of novel therapeutics. These studies will accelerate understanding of how the microbiome can be used to diagnose, stratify patients and treat cancer.
Impact No outputs to date. This is a multidisciplinary collaboration bringing together cancer biology, clinical trials, cancer modelling and immunology.
Start Year 2019
 
Description CRUK Grand Challenge - Manipulating the microbiome to beat cancer 
Organisation Harvard University
Department Harvard T.H. Chan School of Public Health
Country United States 
Sector Academic/University 
PI Contribution My lab is part of the OPTIMISICC consortium that brings together 14 investigators from Canada, The Netherlands, Spain, USA and UK with expertise in genomics, microbiology, genetics, immunology, epidemiology and pathology. The goal is to discover how certain microbes inside the body contribute to cancer development and treatment responsiveness and to harness this knowledge for novel therapeutic approaches. My lab is contributing to experimental characterisation of the interactions between the host and microbiome in driving colorectal cancer, with a focus on the immune response. This includes the identification of bacterial species and functions that promote metastatic colorectal cancer in mouse models, and examining the concurrent key host pathways involved in immune and tissue responses. We will also re-create the complex tumour microenvironment by probing co-culture of immune and stromal cells with patient-derived organoids in the presence or absence of specific microbes and/or metabolite cocktails.
Collaborator Contribution Partners across the collaboration are comparing the gut microbiome from thousands of people at risk of developing bowel cancer to look for associations between the microbiome and cancer development. These studies will also examine the epidemiology of bowel cancer and microbiome characteristics, as well as the localisation of bacteria within the tumour. The research aims to develop, test and implement microbiome-targeted therapeutic approaches for colorectal cancer through analysis of cancer models, pre-clinical development and clinical trials of novel therapeutics. These studies will accelerate understanding of how the microbiome can be used to diagnose, stratify patients and treat cancer.
Impact No outputs to date. This is a multidisciplinary collaboration bringing together cancer biology, clinical trials, cancer modelling and immunology.
Start Year 2019
 
Description CRUK Grand Challenge - Manipulating the microbiome to beat cancer 
Organisation Johns Hopkins University
Country United States 
Sector Academic/University 
PI Contribution My lab is part of the OPTIMISICC consortium that brings together 14 investigators from Canada, The Netherlands, Spain, USA and UK with expertise in genomics, microbiology, genetics, immunology, epidemiology and pathology. The goal is to discover how certain microbes inside the body contribute to cancer development and treatment responsiveness and to harness this knowledge for novel therapeutic approaches. My lab is contributing to experimental characterisation of the interactions between the host and microbiome in driving colorectal cancer, with a focus on the immune response. This includes the identification of bacterial species and functions that promote metastatic colorectal cancer in mouse models, and examining the concurrent key host pathways involved in immune and tissue responses. We will also re-create the complex tumour microenvironment by probing co-culture of immune and stromal cells with patient-derived organoids in the presence or absence of specific microbes and/or metabolite cocktails.
Collaborator Contribution Partners across the collaboration are comparing the gut microbiome from thousands of people at risk of developing bowel cancer to look for associations between the microbiome and cancer development. These studies will also examine the epidemiology of bowel cancer and microbiome characteristics, as well as the localisation of bacteria within the tumour. The research aims to develop, test and implement microbiome-targeted therapeutic approaches for colorectal cancer through analysis of cancer models, pre-clinical development and clinical trials of novel therapeutics. These studies will accelerate understanding of how the microbiome can be used to diagnose, stratify patients and treat cancer.
Impact No outputs to date. This is a multidisciplinary collaboration bringing together cancer biology, clinical trials, cancer modelling and immunology.
Start Year 2019
 
Description CRUK Grand Challenge - Manipulating the microbiome to beat cancer 
Organisation Royal Netherlands Academy of Arts and Sciences
Department Hubrecht Institute
Country Netherlands 
Sector Academic/University 
PI Contribution My lab is part of the OPTIMISICC consortium that brings together 14 investigators from Canada, The Netherlands, Spain, USA and UK with expertise in genomics, microbiology, genetics, immunology, epidemiology and pathology. The goal is to discover how certain microbes inside the body contribute to cancer development and treatment responsiveness and to harness this knowledge for novel therapeutic approaches. My lab is contributing to experimental characterisation of the interactions between the host and microbiome in driving colorectal cancer, with a focus on the immune response. This includes the identification of bacterial species and functions that promote metastatic colorectal cancer in mouse models, and examining the concurrent key host pathways involved in immune and tissue responses. We will also re-create the complex tumour microenvironment by probing co-culture of immune and stromal cells with patient-derived organoids in the presence or absence of specific microbes and/or metabolite cocktails.
Collaborator Contribution Partners across the collaboration are comparing the gut microbiome from thousands of people at risk of developing bowel cancer to look for associations between the microbiome and cancer development. These studies will also examine the epidemiology of bowel cancer and microbiome characteristics, as well as the localisation of bacteria within the tumour. The research aims to develop, test and implement microbiome-targeted therapeutic approaches for colorectal cancer through analysis of cancer models, pre-clinical development and clinical trials of novel therapeutics. These studies will accelerate understanding of how the microbiome can be used to diagnose, stratify patients and treat cancer.
Impact No outputs to date. This is a multidisciplinary collaboration bringing together cancer biology, clinical trials, cancer modelling and immunology.
Start Year 2019
 
Description CRUK Grand Challenge - Manipulating the microbiome to beat cancer 
Organisation University of British Columbia
Department Canada's Michael Smith Genome Sciences Centre
Country Canada 
Sector Academic/University 
PI Contribution My lab is part of the OPTIMISICC consortium that brings together 14 investigators from Canada, The Netherlands, Spain, USA and UK with expertise in genomics, microbiology, genetics, immunology, epidemiology and pathology. The goal is to discover how certain microbes inside the body contribute to cancer development and treatment responsiveness and to harness this knowledge for novel therapeutic approaches. My lab is contributing to experimental characterisation of the interactions between the host and microbiome in driving colorectal cancer, with a focus on the immune response. This includes the identification of bacterial species and functions that promote metastatic colorectal cancer in mouse models, and examining the concurrent key host pathways involved in immune and tissue responses. We will also re-create the complex tumour microenvironment by probing co-culture of immune and stromal cells with patient-derived organoids in the presence or absence of specific microbes and/or metabolite cocktails.
Collaborator Contribution Partners across the collaboration are comparing the gut microbiome from thousands of people at risk of developing bowel cancer to look for associations between the microbiome and cancer development. These studies will also examine the epidemiology of bowel cancer and microbiome characteristics, as well as the localisation of bacteria within the tumour. The research aims to develop, test and implement microbiome-targeted therapeutic approaches for colorectal cancer through analysis of cancer models, pre-clinical development and clinical trials of novel therapeutics. These studies will accelerate understanding of how the microbiome can be used to diagnose, stratify patients and treat cancer.
Impact No outputs to date. This is a multidisciplinary collaboration bringing together cancer biology, clinical trials, cancer modelling and immunology.
Start Year 2019
 
Description CRUK Grand Challenge - Manipulating the microbiome to beat cancer 
Organisation University of Guelph
Country Canada 
Sector Academic/University 
PI Contribution My lab is part of the OPTIMISICC consortium that brings together 14 investigators from Canada, The Netherlands, Spain, USA and UK with expertise in genomics, microbiology, genetics, immunology, epidemiology and pathology. The goal is to discover how certain microbes inside the body contribute to cancer development and treatment responsiveness and to harness this knowledge for novel therapeutic approaches. My lab is contributing to experimental characterisation of the interactions between the host and microbiome in driving colorectal cancer, with a focus on the immune response. This includes the identification of bacterial species and functions that promote metastatic colorectal cancer in mouse models, and examining the concurrent key host pathways involved in immune and tissue responses. We will also re-create the complex tumour microenvironment by probing co-culture of immune and stromal cells with patient-derived organoids in the presence or absence of specific microbes and/or metabolite cocktails.
Collaborator Contribution Partners across the collaboration are comparing the gut microbiome from thousands of people at risk of developing bowel cancer to look for associations between the microbiome and cancer development. These studies will also examine the epidemiology of bowel cancer and microbiome characteristics, as well as the localisation of bacteria within the tumour. The research aims to develop, test and implement microbiome-targeted therapeutic approaches for colorectal cancer through analysis of cancer models, pre-clinical development and clinical trials of novel therapeutics. These studies will accelerate understanding of how the microbiome can be used to diagnose, stratify patients and treat cancer.
Impact No outputs to date. This is a multidisciplinary collaboration bringing together cancer biology, clinical trials, cancer modelling and immunology.
Start Year 2019
 
Description CRUK Grand Challenge - Manipulating the microbiome to beat cancer 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution My lab is part of the OPTIMISICC consortium that brings together 14 investigators from Canada, The Netherlands, Spain, USA and UK with expertise in genomics, microbiology, genetics, immunology, epidemiology and pathology. The goal is to discover how certain microbes inside the body contribute to cancer development and treatment responsiveness and to harness this knowledge for novel therapeutic approaches. My lab is contributing to experimental characterisation of the interactions between the host and microbiome in driving colorectal cancer, with a focus on the immune response. This includes the identification of bacterial species and functions that promote metastatic colorectal cancer in mouse models, and examining the concurrent key host pathways involved in immune and tissue responses. We will also re-create the complex tumour microenvironment by probing co-culture of immune and stromal cells with patient-derived organoids in the presence or absence of specific microbes and/or metabolite cocktails.
Collaborator Contribution Partners across the collaboration are comparing the gut microbiome from thousands of people at risk of developing bowel cancer to look for associations between the microbiome and cancer development. These studies will also examine the epidemiology of bowel cancer and microbiome characteristics, as well as the localisation of bacteria within the tumour. The research aims to develop, test and implement microbiome-targeted therapeutic approaches for colorectal cancer through analysis of cancer models, pre-clinical development and clinical trials of novel therapeutics. These studies will accelerate understanding of how the microbiome can be used to diagnose, stratify patients and treat cancer.
Impact No outputs to date. This is a multidisciplinary collaboration bringing together cancer biology, clinical trials, cancer modelling and immunology.
Start Year 2019
 
Description CRUK Grand Challenge - Manipulating the microbiome to beat cancer 
Organisation Vall d'Hebron University Hospital
Country Spain 
Sector Hospitals 
PI Contribution My lab is part of the OPTIMISICC consortium that brings together 14 investigators from Canada, The Netherlands, Spain, USA and UK with expertise in genomics, microbiology, genetics, immunology, epidemiology and pathology. The goal is to discover how certain microbes inside the body contribute to cancer development and treatment responsiveness and to harness this knowledge for novel therapeutic approaches. My lab is contributing to experimental characterisation of the interactions between the host and microbiome in driving colorectal cancer, with a focus on the immune response. This includes the identification of bacterial species and functions that promote metastatic colorectal cancer in mouse models, and examining the concurrent key host pathways involved in immune and tissue responses. We will also re-create the complex tumour microenvironment by probing co-culture of immune and stromal cells with patient-derived organoids in the presence or absence of specific microbes and/or metabolite cocktails.
Collaborator Contribution Partners across the collaboration are comparing the gut microbiome from thousands of people at risk of developing bowel cancer to look for associations between the microbiome and cancer development. These studies will also examine the epidemiology of bowel cancer and microbiome characteristics, as well as the localisation of bacteria within the tumour. The research aims to develop, test and implement microbiome-targeted therapeutic approaches for colorectal cancer through analysis of cancer models, pre-clinical development and clinical trials of novel therapeutics. These studies will accelerate understanding of how the microbiome can be used to diagnose, stratify patients and treat cancer.
Impact No outputs to date. This is a multidisciplinary collaboration bringing together cancer biology, clinical trials, cancer modelling and immunology.
Start Year 2019
 
Description Viktor Koelzer, digital pathology 
Organisation University Hospital Zürich
Country Switzerland 
Sector Hospitals 
PI Contribution We are applying digital imaging approaches to detect IL-23 in situ in tissue samples from patients with CRC or IBD.
Collaborator Contribution Viktor Koelzer has been advising us on the development of digital analysis settings using Halo to image activity of the IL-23 gene in tissues. We initiated this collaboration through the S-CORT consortium when Viktor was an pathologist at the University of Oxford and have maintained this partnership with Viktor in his new role as Attending Pathologist and Associate Professor at Zurich University Hospital.
Impact Viktor's imaging expertise has allowed us to progress our analysis of the cellular source of IL-23 and associated tumour associated signalling pathways.
Start Year 2019
 
Title METHOD FOR TREATMENT AND PROGNOSIS OF COLORECTAL CANCER 
Description The invention relates to the treatment and prognosis of colorectal cancer, especially proximal colorectal cancer. It also relates to identifying patients with colorectal cancer who are likely to respond to therapy with an inhibitor of interleukin 22 signalling. 
IP Reference WO2016189282 
Protection Patent application published
Year Protection Granted 2017
Licensed No
Impact none
 
Description 'Dining out with friends' public lecture at University of York (2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Part of the University of York Open Lecture Series open to all members of the University and General Public The lectures aim to capture the imagination of everyone interested in biology.
Year(s) Of Engagement Activity 2016
URL https://www.york.ac.uk/biology/news-events/open-lectures/
 
Description 2016 Edinburgh Science Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I gave a talk and contributed to a panel discussion focussing on gut bacteria and their relationships with our health. The audience asked a broad range of questions exploring diet, faecal transplants, probiotics, antibiotics among many other topics.
Year(s) Of Engagement Activity 2016
URL http://britsocimmblog.org/gut-feeling/
 
Description 2016 Oxfordshire Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Members of my laboratory presented our Gut Reactions exhibit at the Oxfordshire Science Festival. This exhibit includes a magnetic giant gut wall that encourages the public to think differently about the immune cells and bacteria that inhabit out gut.
Year(s) Of Engagement Activity 2016
URL http://www.oxfordshiresciencefestival.com/2016-festival-programme.html
 
Description 2017 Oxfordshire Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact My laboratory displayed our Gut Reactions exhibit to communicate our work to the public. The exhibit models healthy immune-microbe interactions and how this breaks down in disease. The aim is educate the general public about the importance of the gut and our microbiome and to excite children about science.
Year(s) Of Engagement Activity 2017
URL https://www.oxscifest.com/
 
Description BSI annual congress 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact We took our Giant Gut Wall exhibit to the BSI annual conference to inspire others in the immunology community to take part in public engagement.
Year(s) Of Engagement Activity 2019
URL https://www.immunology.org/events/british-society-for-immunology-congress-2019
 
Description Big Bang Fair 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Members of F. Powrie's group were present at the fair displaying a giant magnetic gut wall, to demonstrate the interaction between bacteria in our gut and the immune system. The wall encourages people to think differently about our gut and the part it plays in keeping us healthy. Researchers fwere at hand to discuss the role of different bacteria in the gut and how the group's research is leading international research into the link between gut bacteria and arthritis.
Year(s) Of Engagement Activity 2018
URL https://www.thebigbangfair.co.uk/
 
Description Curiosity Carnival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact My laboratory displayed our Gut Reactions exhibit to communicate our work to the public. The exhibit models healthy immune-microbe interactions and how this breaks down in disease. The aim is educate the general public about the importance of the gut and our microbiome and to excite children about science.
Year(s) Of Engagement Activity 2017
URL http://www.ox.ac.uk/curiosity-carnival/about
 
Description MRC Festival of Medical Research 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact My group participated in Science in the Supermarket organsied by the CRUK/MRC Oxford Institute for Radiation Oncology as part of the MRC Festival of Medical Research 2019
Year(s) Of Engagement Activity 2019
URL https://www.imm.ox.ac.uk/about/news/taking-science-to-the-supermarket
 
Description Microbiome talk at Abingdon Science Club 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact A member of my laboratory gave a presentation on the state of the art of microbiome research to the Abingdon Science Club ATOM
Year(s) Of Engagement Activity 2019
URL https://atomsociety.org.uk/08-2019-microbiota-c-pearson/
 
Description Minerva Lecture Series, University of Bath 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Minerva Lectures are a series of public lectures designed to tackle big questions and share latest insights across a whole range of topics, from future transport to the environment, politics to healthcare.
Year(s) Of Engagement Activity 2018
URL https://www.bath.ac.uk/campaigns/minerva-series-of-lectures/
 
Description NIHR Oxford Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact The open day offers an opportunity for members of the public, patients and their families to find out about some of the world-leading research that's going on at Oxford University Hospitals NHS Foundation Trust, in partnership with the University of Oxford. The Powrie lab presented the Giant Gut Wall which demonstrates in an engaging way how the bacteria that inhabit our bodies impact health and disease. Visitors to the exhibit asked questions and developed a better understanding of how research in the laboratory can lead to new therapies that change lives.
Year(s) Of Engagement Activity 2019
 
Description Pint of Science 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Researchers from F. Powrie's group talked to the public about the microbiome and how it is fundamentally linked to our health and well being, and the positives and negatives our microbiota bring.
Year(s) Of Engagement Activity 2018
URL https://pintofscience.co.uk/event/the-microbiome
 
Description Public Open Day - Celebrating Biomedical Research 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Members of my laboratory took the Gut Reactions exhibit as a method of communicating the BRC's research in the area mucosal immunology and the microbiome to patients and the general public. The exhibit helped visitors understand current research in the area of mucosal immunology and why it is important.
Year(s) Of Engagement Activity 2016
URL https://oxfordbrc.nihr.ac.uk/event/public-open-day-celebrating-medical-research/
 
Description Royal Society Satellite Science Exhibition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Members of my laboratory presented our Gut Reactions exhibit, which includes a magnetic giant gut wall that encourages the public to think differently about the immune cells and bacteria that inhabit out gut. It was estimated that more than 5000 visitors attended the event.
Year(s) Of Engagement Activity 2016
URL https://royalsociety.org/science-events-and-lectures/science-exhibition-manchester/exhibits/youre-ne...
 
Description University of Bath Minerva Public Lecture "Dining out with friends - inflammatory bowel disease" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact This was one of a series of free open lectures organised by the University of York on a wide variety of topics and aimed at a general audience. The audience gained insight into the role of our gut bacteria in human health and disease and how this knowledge might used to develop new treatments for inflammatory disease. The talk stimulated questions and discussion.
Year(s) Of Engagement Activity 2017
URL http://www.bath.ac.uk/about/community/minerva-series-lectures/Powrie
 
Description World Immunology Day 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Fiona Powrie gave a talk at the Francis Crick Institute about how our gut reacts to microbes in heath and disease and discussed how our immune system discriminates between 'good' and 'bad' microbes to maintain gut health.
Year(s) Of Engagement Activity 2018
URL https://www.crick.ac.uk/whats-on/upcoming-events/2018/04/27/world-immunology-day-2018/