Cancer immunotherapy is a breakthrough for some but not all cancers. Our group tries to understand why it is not the case for breast cancer.

The immune system protects the human body against diseases by destroying foreign substances like bacteria and viruses. T-cells, a type of white blood cells, are the active components in this process as they recognize and destroy foreign cells. T-cells can also recognize tumour cells. About thirty years ago, T. Boon and colleagues at the de Duve Institute and Brussels branch of the Ludwig Institute discovered specific markers on the surface of cancer cells (called tumor antigens) that can be recognized by T-cells, which then destroy the tumor cells. This work paved the way for clinical applications of cancer immunotherapy, taking advantage of the tumor-specificity and memory of these T-cells to propose specific and harmless cancer treatments.

In recent years, immunotherapy has emerged as a new modality of cancer treatment. Remarkable results are obtained in patients with advanced metastatic cancer, treated with immunostimulatory antibodies that enhance the activity of anti-tumor T-cells. Many oncologists consider cancer immunotherapy to be at the forefront of the oncology field, as it is clear that patients with a variety of cancers are achieving clinical benefit. However, despite the indisputable clinical successes, the effectiveness of the treatments is still limited in many cases. Our research aims to better understand the mechanisms and limitations of T cell-mediated immunity to human tumors in order to improve the clinical efficacy of cancer immunotherapy.

One line of our research focuses on the specificity and functional properties of the T-cells that are present within human tumors but appear to be quiescent. In breast cancer we have observed that antitumor T cells were often absent from the tumors, which stands in sharp contrast with what we had observed in melanomas. It probably explains why immunostimulatory antibodies do not bring a significant clinical benefit to most patients with breast cancer.

One reason for the paucity of antitumor T cells in breast cancer is the scarcity of tumor antigens in these tumors. In a tumor that contained many antigens we did find antitumor T cells, indicating that tumor-specific T cell responses do occur against breast cancer when the tumor antigenicity is high. We will explore the possibility that antitumor T cell responses develop at an earlier stage of breast cancer development, in the so-called in situ carcinomas. If we detect such responses, immunotherapy for very early stage breast cancers should then consist in immunization against tumor antigens, combined with immunostimulatory antibodies.

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Complete list on PubMed
Pierre Coulie
Institut de Duve
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+32 2 764 75 81
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