Elisabeth M Battinelli, MD, PhD, CRI CLIP Investigator Brigham & Women's Hospital/Harvard Medical School Area of Research: All Cancers The aim of Dr. Battinelli’s research is to demonstrate that cancer patients would benefit from the addition of anti- platelet drugs to their immune checkpoint inhibitor (ICI) regimen. This cross-disciplinary project will directly lead to a clinical trial that combines targeted platelet therapy with ICIs to improve immune therapy outcomes in immunotherapy-refractory patients. Cancer metastasis is a multistep process that depends on detachment of circulating tumor cells from the primary tumor, survival in circulation, colonization, and expansion of new sites of disease. Despite a barrage of destructive forces including immune surveillance, many cancer cells survive the metastasis journey. The guardian of these persistent tumor cells is the platelet, which is the first blood cell tumor cells encounter after leaving the primary tumor and entering circulation. Traditionally viewed as the band-aids of the blood, the contribution of platelets to the progression of malignancy is emerging as a compelling focus for therapeutic intervention. In support of this, patients with an elevated platelet count (thrombocytosis) at time of diagnosis often have a worse prognosis with decreased survival rates. Although ICIs have proven modestly beneficial; immune-refractoriness remains an area of unmet need in cancer. It has been shown that PD-L1 expression on tumor cells can predict response to ICIs. Dr. Battinelli has further obtained evidence that platelet-derived EGF interacts with tumor cell EGFR to upregulate cancer PD-L1 expression, which in turn acts as a negative regulator of the adaptive immune response. This process can be reversed by anti-platelet drugs. She hypothesizes that in cancer, platelets reprogram tumor cells to express increased PD-L1, enabling them to evade immune destruction; and that targeting platelets represents a novel platform for developing less toxic therapies. Dr. Battinelli has designed preclinical studies utilizing anti-platelet agents to block platelet-mediated PD- L1 upregulation. Projects and Grants Targeting platelets to improve immunotherapy response Brigham & Women’s Hospital/Harvard Medical School | All Cancers | 2023
