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Better understanding and use of the immune system

SIRIC team
01/22/2019
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A better understanding of the host-tumor dialogue and its evolution as the disease progresses, including the impact of treatment, should enable us to make better use of the immune system and to improve the therapeutic management of the most aggressive breast cancers.
Immunothérapie

The immunotherapy revolution

Over the past 10 years immunity has been at the heart of much cancer research and the results of this research have led to a veritable paradigm shift in the management of the disease. Immune checkpoint inhibitors have revolutionized the management of cutaneous and lung melanomas. In 2018 the first cell and gene therapies are beginning to be incorporated in oncologists’ therapeutic arsenal.

Despite the immense promise only a small minority of cancer patients are treated with immunotherapy. In breast cancer where the large majority of tumors can be treated with the standard therapeutic arsenal, immunotherapy could be particularly interesting for more aggressive forms.

Triple negative cancers: hopes and limits

Triple negative breast cancer is a very heterogeneous disease at the molecular level. It’s characterized by the presence of p53 mutations (~80%), immune signatures and a high level of neoantigens as well as the presence of lymphocytes. These factors are recognized as being favorable for the use of immune checkpoint inhibitors.

This data suggests that women with triple negative breast cancer can benefit from an immunotherapy treatment. Unfortunately the results so far have shown a moderate response rate.

Understanding and offering new approaches

The first results show that it is essential to better understand the immune response over the course of the disease and treatment. It’s equally important to be able to rapidly identify patients who will respond to immunotherapies as well as those for whom these treatments will be useless and for whom new therapeutic approaches are needed.

In this context we propose 3 research projects focusing on immunology, the functioning of tumor microenvironment as well as DNA repair pathways and also the command of innovative single cell analysis techniques.

  1. Immune checkpoint inhibitors and the evolution of the T cell repertoire
  2. Interaction between cancer-associated fibroblasts and immune infiltrate
  3. Combination therapy: immunotherapy, radiotherapy and DNA repair inhibitors