Resident memory T cells as targets for breast cancer immunotherapy

Project Description:

Triple-negative breast cancer (TNBC) is an aggressive tumour type with a high risk of progression to metastasis and death. Therefore, there is an urgent need to identify better treatments for this disease. Recently, immunotherapy has emerged as an effective way to destroy cancer cells by boosting the body’s own immune system to destroy tumours, but more work is needed to improve the effectiveness of immunotherapy in breast cancer. Checkpoint blockade is one type of immunotherapy that aims to improve the ability of CD8+ T cells, a special type of immune cell, to seek out and destroy cancer cells, but currently has limited efficacy in TNBC. Prof Laura Mackay and team have identified a type of CD8+ T cell, called tissue-resident memory T cell and found that TNBC patients with more tissue-resident memory T cells have better prognosis and higher survival outcome. Here, the team will seek to understand the genes and proteins that make these cells most effective at killing tumours to design a novel immunotherapy treatment strategy.

Why is this work needed:

Triple-negative breast cancers (TNBC) accounts for up to 15% of all breast cancers, are aggressive, spread fast, and result in poor patient responses to treatments like chemotherapy and radiation therapy. Immunotherapy is a relatively newer form of treatment that acts to stimulate cancer-fighting immune cells to kill cancer cells. While immunotherapy has been successful in the treatment of certain blood cancers, is yet to show efficacy in the treatment of solid cancers, like breast cancer. Hence there is a need to develop novel and more effective methods to reinvigorate a patient’s own immune response to fight the cancer to help lower the breast cancer death rate.

Expected outcomes:

Successful outcomes of this study will reveal ways to empower tissue-resident memory T cells to effectively seek and destroy cancer cells as a novel treatment option for TNBC patients who have one of the poorer prognoses amongst all the breast cancer types

Project description:

Triple-negative breast cancer (TNBC), which is an aggressive tumour type with a higher risk for metastasis and poorer prognosis, accounts for up to 15% of breast cancers. Tumour resection surgery, chemotherapy and radiotherapy remain standard treatments for TNBC. It’s now widely acknowledged that immunotherapy which harnesses and reprograms the body’s own immune system can be a powerful way to specifically target and eliminate cancer. Immunotherapy works by boosting cancer-fighting immune cells called CD8+ T cells. However, some CD8+ T cells within a tumour become “exhausted” and lose their ability to kill the tumour. Prior research by Prof Laura Mackay at the University of Melbourne and colleagues have identified a specific type of CD8+ T cells known as tissue-resident memory T cells, and found that TNBC patients with higher levels of tissue-resident memory T cells tend to have better prognosis and higher survival outcome.

In this NBCF-funded study the team aims to examine a novel approach of eradicating cancer cells by enhancing the population of tissue-resident memory T cells, instead of reviving exhausted T cells, currently one of the strategies used to improve immunotherapy. The approach will seek to understand the genes and proteins that make these cells most effective at killing tumours with the aim to use this knowledge to design more effective immunotherapy strategies for TNBC which currently faces limited effective treatment options.