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Understanding the effects of obesity in Triple Negative Breast Cancer (TNBC) to improve responses to immunotherapy

Published: 05/8/22 7:00 AM

Monash University Professor

Tony Tiganis

Project Description: There is now compelling evidence that obesity is a key factor in the progression of many human malignancies, including breast cancer. In particular, more women with triple negative breast cancer (TNBC) are overweight or obese than normoweight, and obese patients with TNBC have a poorer prognosis. Although there are many mechanisms by which obesity may impact on the development of solid malignancies such as TNBC, a key mechanism may involve subverting the immune system’s ability to recognise and destroy tumour cells. Recent clinical trials have shown that approaches that enhance the immune system’s ability to fight cancer (immunotherapies) can be effective in combating TNBC. This project aims to understand how obesity influences TNBC and to develop new ways by which to sensitise these patients to immunotherapy.  

Why This Work is Needed: TNBC accounts for 15-20% of all breast cancer cases. It is one of the most aggressive forms of breast cancer with the poorest outcomes, with worse overall survival reported for those who are obese. Hence new, and effective therapies for these patients are clearly needed. 

Expected Outcomes: This study will yield insights into the molecular mechanisms by which obesity influences the development of TNBC and how it may affect immunotherapy in this patient cohort. This project will also define innovative approaches for the use of immunotherapy to treat obese TNBC patients. 

Project Details

TNBC is a highly aggressive type of breast cancer with limited treatment options and is more likely to recur compared to hormone receptor positive breast cancers. Patients diagnosed with TNBC in general have poorer overall survival outcomes compared to other types of breast cancer. Obese women with TNBC have the poorest prognosis of all breast cancer patients. 

Immunotherapy, which harnesses the body’s own immune system to fight the cancer, has shown promise in TNBC clinical trials. However, preclinical studies in mouse models indicate that obesity may diminish the effectiveness of immunotherapy in TNBC by hindering the recruitment of cancer-fighting immune cells.  

This study led by Professor Tony Tiganis, from Monash University, aims to investigate the mechanisms by which obesity affects the recruitment and activation of immune cells to contribute to TNBC progression. Obese individuals have elevated levels of the stress hormone cortisol and the feeding hormone leptin in their blood. Preliminary data from the team has shown that abnormal levels of these hormones decrease the number of cancer-fighting immune cells capable of infiltrating into the tumour to destroy it. 

With the use of tumour samples from TNBC patients, new drivers of TNBC growth that are elevated in obese patients will be investigated and evaluated in mouse models. Combination immunotherapy with drugs that block the action of cortisol and leptin will also be tested in mouse models to determine if they can sensitise obese TNBC patients to immunotherapy. The overall goal of this study is to improve the effectiveness of immunotherapy for a group of breast cancer patients with the poorest outcomes. 

Monash University Professor

Tony Tiganis