Enhancing the body’s ability to recognize and eliminate triple negative breast cancer cells

Project Description:

Triple negative breast cancer (TNBC) is an aggressive form of cancer with a high tendency to spread to other organs making it difficult to treat thus resulting in the lowest survival outcomes relative to other breast cancer subtypes. The immune system is known to play a critical role in detecting and eliminating breast cancer cells. However, A/Prof Joy Wolfram and colleagues have previously shown that TNBC cells release extracellular vesicles (harmful biomolecular packages) that help TNBC cells avoid detection and destruction by the immune system. In this NBCF-funded study the team aims to investigate how these extracellular vesicles affect the function of immune cells and how this impacts the ability of the immune cells to destroy breast cancer cells. Moreover, using TNBC preclinical models, the team will apply this newfound knowledge to explore approaches for targeting extracellular vesicles to overcome immune cell suppression and to treat breast cancer more effectively.

Why is this work needed:

TNBC is an aggressive form of cancer, with poor survival outcomes. Currently, the most common therapies for TNBC are chemotherapies, which have toxic side effects, and immune therapies which, currently, only benefit small numbers of patients. Hence there is a need to gain a better understanding of the aggressive features of TNBC cells to help develop new treatment strategies to reduce deaths from TNBC.

Expected outcomes:

Successful outcomes of this study will reveal how extracellular vesicles released by TNBC cells prevent immune cells from finding and destroying cancer cells. A better understanding of the interactions and cell-to-cell communication between TNBC and immune cells is critical for developing effective therapies and reduce deaths from this disease.

Project description:

Triple negative breast cancer (TNBC) is a particular aggressive type of breast cancer, with the highest rate of recurrence, limited treatment options and overall poor survival outcomes compared to other types of breast cancer. TNBC accounts for up to 15% of all breast cancer cases and in Australia this equates to around 3000 new cases of TNBC every year.

The immune system protects the body from infections and diseases and natural killer (NK) cells are immune cells capable of detecting and killing cancer cells. However, a key feature of tumour development is immunoevasion, where cancer cells weaken the activity of immune cells allowing cancer cells to survive and spread to other organs in the body. Cells communicate with its neighbouring or distant cells via the release of extracellular vesicles. These small packages transport bioactive cargo and are used to deliver messages.

Prior research led by A/Prof Joy Wolfram at the University of Queensland has demonstrated that TNBC cells secrete harmful extracellular vesicles that impair the function of NK cells, facilitating the cancer’s survival and metastatic dissemination.

With NBCF support, the team aims to examine the molecular composition of extracellular vesicles released by TNBC cells and understand how these specific vesicle-associated molecules transmit messages to compromise the function of NK cells. This knowledge will be used to target cancer-secreted extracellular vesicles aiming at restoring the NK cells cancer-killing capacity.