Identification of Immunological Biomarkers Predictive of Pathological Response in Triple Negative Breast Cancer Patients Undergoing Neo-adjuvant Chemotherapy
Prof Bernardo Rapoport
Title of the project
Identification of immunological biomarkers predictive of pathological response in triple negative breast cancer patients undergoing neo-adjuvant chemotherapy.
It is now well recognised that inappropriate, chronic activation of the human innate immune system promotesepithelial malignancies, while tumour cells per se not only suppress the reactivity of tumour-targeted T cells, butmay also utilise immune-derived mediators to enhance tumour growth and metastasis. These insights, in turn,have revitalised interest in the development of novel, broadly-active immunotherapies which counteract theimmunosuppressive activities of tumour cells. Foremost among these are immunotherapeutic approaches whichtarget negative immune checkpoint molecules and growth-promoting cytokines/chemokines. Although triple-negative breast cancer (TNBC) is recognised as being potentially amenable to these therapies, additional research is required to extensively characterise the cellular and humoral immunological biomarker profiles of those patients who are responsive or unresponsive to conventional chemotherapy. This important topic represents the basis of the proposed study which is focused on establishing: i) the profiles and concentrations of soluble, systemic biomarkers of tumour-associated immuno suppression; ii) expression of ligands for negative immune checkpoint molecules by tumour cells in situ; iii) immunophenotyping to characterise the types of tumour-infiltrating immune cells in patients with untreated TNBC; and iv) the immuno suppressive potential of tobacco usage. This information will then be correlated with the responsiveness of patients to neo-adjuvant chemotherapy to identify those biomarkers, both cellular and humoral, which best predict outcome, as well as those which represent potential targets for immunotherapy.