Immune system tolerogenicity and cancer
Research type
Research Study
Full title
Immune system tolerogenicity and cancer
IRAS ID
283778
Contact name
Masashi Narita
Contact email
Sponsor organisation
University of Cambridge
Clinicaltrials.gov Identifier
NA, NA
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Our bodies are made of cells: liver cells, muscle cells, brain cells etc. We have evolved such that all of the cells within our bodies contain the necessary genetic information, DNA, to copy themselves (to replicate). An unfortunate consequence of this is that any cell has the potential to replicate when it shouldn’t and to form a cancer. However, there are some inbuilt limits so that cells cannot replicate indefinitely. Senescence refers to a stable arrest of cell replication, in effect the cells go to sleep instead of forming a cancer. The activation of cancer causing genes (oncogenes) may lead to a premature senescence / cell sleeping, known as Oncogene-Induced Senescence (OIS). The process of senescence restricts cellular replication, in the cells in which it occurs at least. OIS cells are now known to secret signals, which recruit white blood cells (immune cells) to eliminate the OIS cells. Inefficient clearance of OIS cells and their accumulation within the tissue may result in an increased risk of malignant transformation.
We are currently studying liver cancer. Tissue resident macrophages (TRMs)(macrophages are immune cells which eat other cells) within the liver (Kupffer cells, KCs) play a key role in liver tolerogenicity by inhibiting the activation of a special kind of immune cell called a T cell. In this project we aim to study the interaction between KCs and T cells in more depth. We believe that understanding this complex interplay between tissue tolerogenicity and T cells would open a new therapeutic window for modulation of OIS and other senescence/age-associated disorders. Although we are currently studying this in the context of the liver, TRMs exist in nearly all tissues and so our findings may well be more widely applicable to other organs.
REC name
South Central - Berkshire Research Ethics Committee
REC reference
20/SC/0309
Date of REC Opinion
4 Aug 2020
REC opinion
Favourable Opinion