Cancer Immunology
We explore how the interaction between cancer cells and immune cells in the tumour microenvironment impairs immune control of cancer, and how this knowledge could develop new forms of immunotherapy.
Our work
Treatment of cancer patients with immune check point inhibitors and with gene-engineered T cells has improved outcome for many patients. Research at the IIT aims to further understand how the interaction between cancer cells and immune cells in the tumour microenvironment can impair immune control of cancer, and how we can use this knowledge to develop new forms of immunotherapy.
We have a particular interest in liver and kidney cancer and work closely with the large clinical cancer services at the Royal Free Hospital.
Exploring ways to treat kidney cancer using patients’ own cells
IIT researchers led by Prof. Claudia Mauri are collaborating with GSK to discover innovative new kidney cancer treatments that use the patient's own cells.
Projects
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
Clinical trials
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
Our experts
Viral Immunology
Cellular & Molecular Virology
Immunology
Immunology
Computational Biology
Infection and Immunity
Urology
Tumour Immunology
Funding and partnerships
Trial seeks improved outcomes after liver cancer surgery
A study led by Professor Tim Meyer is investigating whether a combination of drugs could help patients with liver cancer.
Selected publications
- Degirmencay A, Thomas S, Holler A, Burgess S, Morris EC, Stauss HJ (2024). Exploitation of CD3ζ to enhance TCR expression levels and antigen-specific T cell function. Front Immunol. 2024 May 30;15: 1386132.
- Arellano-Ballestero H, Zubiak A, Dally C ... Tran MGB, Sabry M, Peppa D, Lowdell MW (2024). Proteomic and phenotypic characteristics of memory-like natural killer cells for cancer immunotherapy. J Immunother Cancer. 2024 Jul 20;12(7): e008717.
- Baker AM, Nageswaran G, Nenclares P ... Chain B, Graham TA (2024). FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA. Cancer Res. 2024 May 15;84(10): 1560-1569.
- Degirmencay A, Thomas S, Mohammed F, Willcox BE, Stauss HJ (2023). Modifications outside CDR1, 2 and 3 of the TCR variable β domain increase TCR expression and antigen-specific function. Front Immunol. 2023 Apr 12;14: 1148890.
- Treger TD, Lawrence JEG, Anderson ND ... Tran M, Behjati S, Chowdhury T (2023). Targetable NOTCH1 rearrangements in reninoma. Nat Commun. 2023 Sep 25;14(1): 5826.
- Li R, Ferdinand JR ... Tran MGB, et al (2022). Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer. Cancer Cell. 2022 Dec 12;40(12): 1583-1599.e10.
- Neves JB, Roberts K ... Stauss H, Tran MGB, Mitchell T (2022). Defining the origin, evolution, and immune composition of SDH-deficient renal cell carcinoma. iScience. 2022 Oct 17;25(11): 105389.
- Zakeri N, Hall A, Swadling L, Pallett LJ ... Maini MK (2022). Characterisation and induction of tissue-resident gamma delta T-cells to target hepatocellular carcinoma. Nat Commun. 2022 Mar 16;13(1): 1372.
- Schmidt NM, Wing PAC, Diniz MO, Pallett LJ, Swadling L ... Maini MK (2021). Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint. Nature Comms 2021 May14;12(1): 2814
- Au L, Hatipoglu E ... Chain B, et al (2021). Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma. Cancer Cell. 2021 Nov 8;39(11): 1497-1518.e11.
- Joshi K, de Massy MR, Ismail M ... Chain B (2019). Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer. Nat Med. 2019 Oct;25(10): 1549-1559. Erratum in: Nat Med. 2020 Jul;26(7): 1148.
- Thomas S, Mohammed F, Reijmers RM … Chain BM, Heemskerk MHM, Morris EC, Willcox BE, Stauss HJ (2019). Framework engineering to produce dominant T cell receptors with enhanced antigen-specific function. Nat Commun. 2019 Oct 1;10(1):4451.
- Frampton D, Schwenzer H ... Chain B ... Fassati A (2018). Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor. Cancer Cell. 2018 Apr 9;33(4): 620-633.e6.
- Fassati A (2018). What a dog transmissible tumor can teach us about cancer regression. Mol Cell Oncol. 2018 Aug 6;5(4): e1472059.
- Easom NJW, Stegmann KA, Swadling L, Pallett LJ ... Maini MK (2018). IL-15 Overcomes Hepatocellular Carcinoma-Induced NK Cell Dysfunction. Front Immunol. 2018 May 9;9:1009. doi: 10.3389/fimmu.2018.01009.
- Fassati A, Mitchison NA (2010). Testing the theory of immune selection in cancers that break the rules of transplantation. Cancer Immunol Immunother. 2010 May;59(5): 643-51.
Cancer forum brings together researchers and clinicians
Cancer forum brings together researchers and clinicians
The second cancer forum encouraging links between clinicians at the Royal Free London and researchers in the UCL Institute of Immunity and Transplantation took place in May 2024 at the Pears Building.
