Identification of breast cancer subtype-specific tumour proteins using lymph nodes of women with early breast cancer

The immune system plays an integral and complex role in breast cancer biology. There is much more that needs to be understood of the role of the immune system in the development of breast cancer in order to harness its potential in the early detection, prevention and treatment of the disease.

A critical part of the immune system is the lymphatic system which is responsible for maintaining fluid levels in the body as well as draining molecules (antigens) shed from bacteria and other microbes from body tissues and delivering them to the lymph nodes. Within the lymph nodes an immune response is generated resulting in killer cells and molecules (antibodies) that are released into the blood stream to kill these invaders. In the same way, cancer cells release antigens that get trapped inside lymph nodes, making it an ideal site for understanding the earliest stages of breast cancer.

It has been established that some molecules are altered in cancer cells and recognised by the immune system as foreign entities these are called tumour-associated antigens (TAAs). TAAs are expressed by malignant cells during tumour progression, and are recognised by a patient’s immune system, in some cases several years prior to the manifestation of clinical symptoms. They prompt the production of cancer-specific antibodies that are generated in the lymph nodes, before being released into the blood stream.

The antibodies are produced very early during tumour growth, often before a tumour is even visible, making them the most sensitive way to identify cancers at an early stage. Previous attempts, using blood antibodies to identify the critical TAAs for cancer diagnosis, have failed due to the presence of too many other unrelated antibodies in the bloodstream.

The research being led by Associate Professor Elgene Lim from the Garvan Institute, in collaboration with Latrobe University, will provide a better understanding of the role the immune system plays in breast cancer, and could inform more targeted use of immunotherapies for treatment. It’s particularly exciting because for immunotherapy to be successful the tumour needs to be targeted at the earliest stage, before immune evasion strategies evolve.

A/Prof Meeusen has developed a process that captures TAA-specific antibodies directly from the lymph node, before they are released into the blood. They believes this approach will make the breast cancer-specific TAAs visible amongst the other irrelevant matter in the blood and it will be the first time TAAs relevant to early stage breast cancer are identified.

Through this novel approach of harnessing the local immune response, this project aims to identify the TAA profile of different breast cancer subtypes (Estrogen receptor (ER) positive, HER2-amplified and triple negative breast cancer), to enable a better understanding of the immune response of breast cancer, according to subtype. It can also reveal potential new biomarkers for early and sub-types of breast cancer, which could have an important impact on earlier diagnosis and treatment of breast cancer.

The potential applications include the development of a sensitive and subtype-specific blood test for breast cancer diagnosis, for which there are currently no blood-based tests, and a better knowledge of the more effective use of immune-based therapies in breast cancer.