August 2019

Unravelling the association between immune senescence and the development of cutaneous squamous cell carcinoma in renal transplant recipients.

Dr Matthew Bottomley is training as a kidney physician at the Oxford Transplant Unit and is a Lecturer in Renal Medicine.  He works in the Transplantation Research and Immunology Group (TRIG), in the Nuffield Department of Surgical Sciences at the University of Oxford.

Background:

Kidney transplantation is one of many medical success stories from the twentieth century. 

Improvements in the surgery itself and the care and medications given after transplant mean that a kidney transplanted into another person today would be likely to keep working for at least fifteen years, allowing that person to live a relatively normal and healthy life in that time.

Unfortunately, many patients who receive a kidney transplant (‘kidney transplant recipients’) still suffer with health problems later on.  One major issue that patients experience is cancer; particularly a type of skin cancer called ‘cutaneous squamous cell carcinoma’ (cSCC).  Around a quarter of kidney transplant recipients will have developed a least one cSCC by twenty years after their transplant. cSCC after transplant can grow more rapidly compared to patients without a transplant and requires urgent surgery to remove.  If left untreated, the cancerous cells spread to other organs in the body and this is generally not treatable. Transplant recipients can develop multiple cSCC over time and require many rounds of surgery to different parts of their body.  cSCC occurs for many reasons, including ultraviolet (UV) radiation exposure and potentially because of some viruses that can infect the skin.  We suspect that the increased risk of cSCC in transplant recipients is also partly because of the tablets taken to dampen down the immune system (immunosuppression) and prevent transplant rejection – we think this also makes the immune system less efficient at killing cells that develop the early signs of cancer.

We have previously found that we can look at the immune cells found in the blood to identify kidney transplant recipients who might be at increased risk of future problems, such as cSCC.  We can detect changes in these immune cells that are also seen in the general population as the immune system grows older and less efficient (an effect we call ‘immune senescence’). Transplant recipients who have evidence of established immune senescence in their immune cells seem to be at increased risk of developing cSCC and may develop another cSCC earlier, compared to transplant recipients without evidence of this process.

Ongoing work:

The grant from the British Skin Foundation will enable us to explore how immune senescence might lead to some kidney transplant recipients suffering with cSCC more than others. 

We will look in more depth at the immune cells in the blood of transplant recipients with immune senescence, to see how well they are able to recognise cell markers associated with cancer and kill cells. We will look at the signals sent out by these cells to communicate with other immune cells (called ‘cytokines’) to see if these are altered in patients with immune senescence. Finally, we will look inside samples of cSCC removed from transplant recipients with and without signs of immune senescence and from cSCC of patients without a transplant to see whether the immune cells within the cancer itself show alterations that mean they are less able to kill cancerous cells.

How this research may help patients:

Increasing our understanding of how changes in the immune system alter our body’s ability to prevent cancer may allow us to identify patients who are at increased risk of cSCC in the future. This may allow us to intervene early in order to reduce the risk of patients developing cSCC.

Our work may also help us to understand why cSCC occurs in some patients and identify new treatment options for patients with cSCC, to improve the immune system’s ability to fight cancer.

Dr Matthew Bottomley

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