Immune receptor proves a promising target to reduce gut inflammation in chemotherapy patients

By / 12th of January, 2015

BETWEEN 60-80% of patients treated with chemotherapy experience debilitating side effects in the gut, depending on the dosage and type of chemotherapy used.

PhD researchers at the University of Adelaide have found that blocking a certain immune receptor reduces the incidence of gut toxicity and signs of pain.

In a paper published in the journal Cancer Treatment Reviews, the research team said their findings could lead to a treatment method to counteract the side effects.

"While the treatment of the cancer itself is usually seen to be of prime importance, chemotherapy can and does have severe side effects for patients – such as diarrhoea, abdominal pain and in some cases, sepsis," says PhD student and lead author of the paper, Hannah Wardill.

"Treatment for these symptoms is limited and often not effective. Side effects of chemotherapy can cause multiple, co-existing health problems which greatly reduce the patient's quality of life and impact on the long term outlook for patients," she says.

Ms Wardill says the gut – one of the areas that is worst affected by chemotherapy – is the biggest organ in the body that is involved in generating an immune response, and growing evidence shows it can impact on the central nervous system.

"Our research has focused on the immune receptor known as Toll-Like receptor 4 (TLR4), which has been implicated not only in the development of gastrointestinal symptoms, but also appears to control people's sensitivity to pain.

"In our laboratory studies, we found that TLR4 sets up an inflammatory response that is exacerbated by chemotherapy. By knocking out the TLR4 receptor, we saw improvements across all key markers of gut toxicity as well as signs of reduced pain," she says.

Fellow PhD student and a co-author on the paper, Ysabella Van Sebille, says toxicity from chemotherapy continues to be under reported.

"Toxicities associated with chemotherapy are a major concern within the field of supportive care in cancer, but we still don't understand the full extent of the problem. Our research has highlighted the potential to treat multiple side effects of chemotherapy by targetting TLR4, which if successful could streamline symptom management," she says.

"The ultimate aim of our studies is to help find a way to mitigate the adverse health problems caused by chemotherapy, which could lead to improved overall care for cancer patients. So far, TLR4 seems to be a promising target for further research."

Key contacts

Hannah Wardill PhD Student School of Medical Sciences, The University of Adelaide
61 422 364 257 hannah.wardill@adelaide.edu.au www.adelaide.edu.au
Ysabella Van Sebille PhD Student School of Medical Sciences, The University of Adelaide
61 422 926 255 ysabell.vansebille@adelaide.edu.au www.adelaide.edu.au