Cancer Immunology

Together with a network of collaborators across UK and Europe, we are using our biobank of samples and range of cutting-edge models to determine how hepatocellular carcinoma exploits the tolerogenic liver niche to escape anti-tumour immunity and to define tractable pathways to overcome this immunosuppressive niche.

Lead Investigator

• Professor Mala Maini (Institute of Immunity & Transplantation, UCL)

Collaborators

• Dr Mariana Diniz (Institute of Immunity & Transplantation, UCL)
• Professor Tim Meyer (Cancer Institute & Institute of Immunity & Transplantation, UCL)
• CRUK HUNTER Accelerator Network (led by Professor Helen Reeves; University of Newcastle)

Funding

• CRUK HUNTER Accelerator Award
• Wellcome Translational Partnership (TIN) Award

Building on our previous experience sampling compartmentalised hepatic immunity by minimally invasive fine needle aspiration (FNA), we are pioneering their use in hepatocellular carcinoma (HCC). We find FNA can comprehensively sample the tumour immune landscape in HCC, paving the way to monitor local immunotherapy responses to guide early stopping/switching and novel target identification.

Lead Investigator

• Professor Mala Maini (Institute of Immunity & Transplantation, UCL)

Collaborators

• Professor Tim Meyer (Cancer Institute & Institute of Immunity & Transplantation, UCL)
• Dr Edward Green (Radiology, Royal Free Hospital)

Funding

• CRUK HUNTER Accelerator Award

Melanoma and other primary cancers have a worse prognosis and response to checkpoint inhibitors when they metastasise to the liver compared to other sites. We are exploring how liver metastases co-opt with the local stromal network to drive immunosuppression and promote tumour progression.

Lead Investigator

• Professor Mala Maini (Institute of Immunity & Transplantation, UCL)

Collaborators

• Dr Rebecca Lee (Wellcome Clinical Fellow, The Francis Crick Institute, London)
• Professor Erik Sahai (The Francis Crick Institute, London)
• Dr Laura Pallett (Institute of Immunity & Transplantation, UCL)
• Dr Mariana Diniz (Institute of Immunity & Transplantation, UCL)
• Professor Derek Mann (University of Newcastle)

Funding

• Wellcome Early Career Award

We are investigating how a mammalian cancer has evolved to become transmissible and bypass the histocompatibility barrier. We are using this model to understand barriers to organ transplantation and how these can be overcome.

Lead Investigator

• Professor Ariberto Fassati (Institute of Immunity & Transplantation, UCL)

Collaborators

• Dr Clare Bennett (Cancer Institute, UCL)
• Professor George Kassiotis (The Francis Crick Institute, London)

Funding

• The Government of Saudi Arabia

Kidney cancer is the 7th most common cancer type in the UK. We aim to study the importance of regulatory B cells (Bregs) in the suppression of the immune system in kidney cancer, which may prevent tumour clearance and result in poor prognosis. We will also determine how the tumour microenvironment promotes Breg recruitment and differentiation while inhibiting effector B cell responses.

Lead Investigator

• Professor Claudia Mauri (Institute of Immunity & Transplantation, UCL)

Co-Investigators

• Professor Hans Stauss (Institute of Immunity & Transplantation, UCL)
• Professor Maxine Tran (Institute of Immunity & Transplantation, UCL)

Funding

• GlaxoSmithKline

We are developing the tools and building the conceptual framework on which to base a quantitative immunology, focusing especially on the role of T cells. T cells have a critical role in immunity, especially in controlling cancer, and many chronic infections. We aim to gain a better quantitative understanding of T cell function, in the context of cancer (e.g. lung, renal, haemopoietic) and in infectious diseases, especially tuberculosis. We use T cell receptor sequences (often referred to as the T cell receptor repertoire) to track clonal expansion and retraction, as tumours progress and regress. We combine this T cell receptor information with other multiomics data sets to build mathematical models of tumour/T cell interactions, which can be used to explore the dynamics of the system and predict outcome of therapeutic interventions.

Lead investigators

• Professor Benny Chain (Institute of Immunity & Transplantation, UCL)
• Dr Andreas Tiffeau-Mayer (Institute of Immunity & Transplantation, UCL)

Collaborators

• Professor Charles Swanton (Francis Crick Institute)
• Professor Sergio Quezada (UCL Cancer Institute)
• Professor Kwee Yong (UCL Cancer Institute)
• Dr Maxine Tran (Institute of Immunity & Transplantation, UCL)
• Dr Yaron Antebi (Weizmann Institute, Israel)

Funding

• Cancer Research UK
• Wellcome Trust
• Rosetrees Foundation

The natural history of kidney cancer has an initial indolent phase, which may last many years, before progression. Our work focuses on the role of key components of the immune microenvironment and critical genomic events in early, mid and late stage sporadic and inherited forms of kidney cancer. This is part of a wider research programme to improve the understanding and management of kidney cancer.

Lead Investigator

• Professor Maxine Tran (Institute of Immunity & Transplantation, UCL)

Collaborators

• Professor Hans Stauss (Institute of Immunity & Transplantation, UCL)
• Professor Claudia Mauri (Institute of Immunity & Transplantation, UCL)
• Dr Dimitra Peppa (Institute of Immunity & Transplantation, UCL)
• Professor Thomas Mitchell (Cambridge University)
• Dr Sam Behajati (Sanger Institute)
• Professor Christian Frezza (University of Cologne)

Funding

• Cancer Research UK
• GlaxoSmithKline
• Kidney Research UK
• Medical Research Council
• NIHR

Despite success of adoptive T cell therapy for blood cancers, it has been difficult to replicate this in patients with solid cancer, including renal cell cancer (RCC).  We use surgically removed tumour material from RCC patients to study in detail the number and function of tumour-infiltrating T and B cell subsets to uncover mechanisms that lead to impaired function. We use this information to employ gene editing and gene transfer technologies to produce T cells with enhanced anti-cancer activity.
 
Lead Investigator

• Professor Hans Stauss (Institute of Immunity & Transplantation, UCL)

Collaborators

• Professor Maxine Tran (Institute of Immunity & Transplantation, UCL)
• Professor Claudia Mauri (Institute of Immunity & Transplantation, UCL)
• Professor Emma Morris (Institute of Immunity & Transplantation, UCL)

Funding

• UKRI
• EU T2Evolve Consortium
• Turkish Ministry of Education
• Thailand Ministry of Education

NK cells play a critical role in antiviral and antitumour defence. Memory-like NK cells, which exhibit enhanced anti-tumour activity and increased persistence compared to conventional NK cells, can be used therapeutically to promote local immune responses with minimal bystander toxicity. We will utilise in house platforms to expand memory-like NK cells with enhanced trafficking and resilience within the suppressive tumour microenvironment. These populations will be used as off-the-shelf therapies, in combination with existing treatments, to treat a broad spectrum of patients with cancer and viral infections. 

Lead Investigator

• Dr Dimitra Peppa (Institute of Immunity & Transplantation, UCL)

Collaborator

• Professor Mark Lowdell (Research Department of Haematology, UCL)

Funding

• NIH
• Royal Free Charity

We have set up this investigator-led multicentre trial, with intensive blood and tissue immune monitoring, to test the capacity of perioperative blockade of the PD-1 or VEGF pathways (or both) to induce local anti-tumour immunity and prolong recurrence-free survival.

Lead Investigator

• Professor Mala Maini (Institute of Immunity & Transplantation, UCL)

Collaborators

• Professor Tim Meyer (Cancer Institute & Institute of Immunity & Transplantation, UCL)
• Professor Benny Chain (Institute of Immunity & Transplantation, UCL)
• PRIMER-1 investigator network

Funding

• CRUK HUNTER Accelerator Award
• Eisai