Chiara Falcomatà, PhD, Postdoctoral Fellow Icahn School of Medicine at Mount Sinai Area of Research: All Cancers, Pancreatic Cancer Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that lacks efficient therapies. While immunotherapies have been shown to benefit several tumor entities, a major reason for their failure in PDAC is its immunosuppressive tumor microenvironment (TME), composed of pro-tumorigenic immune cells, such as macrophages, and lacking anti-tumorigenic ones, such as T cells. Cancer cells produce messengers that drive not only PDAC progression and treatment resistance, but also shape its TME composition. However, how PDAC cells orchestrate this cancer-protective environment is not known. Dr. Falcomatà hypothesizes that PDAC cell-derived immune signals promote immunosuppression and immune evasion and that their targeting would be beneficial to unleash anti-tumor immunity. She will test if receptors expressed, and soluble factors secreted by PDAC cells act on recruitment and differentiation of pro-tumorigenic immune cells and exclude anti-tumorigenic ones. With the goal to mechanistically identify genes in PDAC cells controlling TME organization, driving tumor progression, and preventing immune-mediated tumor eradication, Dr. Falcomatà will make use of Perturb-map. This technology enables her to alter the function of dozens of genes within a tumor with single-cell resolution and spatial architecture readouts, enabling the study of several genes’ function in parallel. The outcome of these studies will (1) establish the function of hypothesis-selected PDAC-associated genes on tumor growth and immunity, (2) provide potential biomarkers for predicting response to immunotherapy, and importantly, (3) identify actionable therapeutic targets for enhancing anti-tumor immunity. The long-term goal is to translate these findings into effective therapies. Projects and Grants Identifying mechanisms of tumor immune composition control in pancreatic cancer Icahn School of Medicine at Mount Sinai | Pancreatic Cancer | 2023 | Brian D. Brown, PhD
