Tissue-specific recruitment of regulatory T cells in colorectal cancer and liver metastases

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Colorectal cancer is the third most common cancer in the United Kingdom after breast and lung cancer. Colorectal cancer is deadly in one-third of patients due to either spread of the disease to other organs at the time of diagnosis or recurrence of the disease later on. Patients with colorectal cancers containing a large number of lymphocytes (a type of white blood cell) have a better prognosis in terms of improved survival than patients with cancers containing fewer lymphocytes. It is proposed that these lymphocytes represent a favourable response to the cancer by the body's natural immune system. A specific group of lymphocytes known as regulatory T cells can suppress the body's immune response and these are also found in abundance in colorectal cancers. Regulatory T cells in tumours can inhibit other lymphocytes from attacking the tumour. Colorectal cancers would therefore ideally contain lymphocytes attacking the cancer and a minimal number of suppressive regulatory T cells. It is known that lymphocytes, including regulatory T cells, are recruited to different tissues in the body via a network of different molecules known as chemokines and adhesion molecules. Regulatory T cells can also be formed from other lymphocytes, a process known as induction.We propose to focus our research on identifying which homing molecules are present on regulatory T cells and which are important in trafficking these suppressive cells into colorectal cancers. The intention is to be able to block recruitment of regulatory T cells into tumours using inhibitors of homing molecules while at the same time allowing effector (non-suppressive) lymphocytes into the cancer unabated. This provides a means to support the body's natural anti-tumour immune response and would be a new means of treating colorectal cancer. We will also identify other immune cells present in colorectal cancer which may be responsible for inducing regulatory T cells within the cancer tissue.The research will be conducted at the University of Birmingham and Queen Elizabeth hospital and will use tissue obtained from patients operated on for colorectal cancer. Lymphocytes will be extracted from the tissue and the homing molecules present will be analysed. Identified important molecules will be studied in further detail including how the lymphocytes respond differently if the homing molecules are blocked by using drugs.