Tanvi Mandadi
Pronouns: she/her
Research Mentor(s): Yaqing Zhang
Research Mentor School/College/Department: Surgery / Medicine
Program:
Authors: Tanvi Mandadi, Faith Avritt, Marina Pasca di Magliano, Yaqing Zhang
Session: Session 2: 10:00 am – 10:50 am
Poster: 93
Abstract
Pancreatic cancer is a highly fatal disease that while only comprising 3% of cancer cases diagnosed in the US, has a survival rate of only 13% for patients. The significant mortality rates for this cancer stems from challenges in early detection and limited treatment options. The pancreatic ductal adenocarcinoma microenvironment is marked by drastic fibrosis and inflammation and contains a multitude of cell types, especially the tumor-associated macrophages (TAMs). TAMs are key contributors to the progression and metastasis of the cancer and are widely present in the tumor microenvironment. In order to distinguish and target the pro-tumor functions of TAMs, we established an in vitro model, namely the tumor-educated macrophages (TEMs), by polarizing bone marrow-derived macrophages (BMDMs) with tumor conditioned media over 5 days. These cells were later harvested and extracted for RNA evaluate activation makers or pro-tumor factors of pancreatic TEMs. We also collected TEM media for metabolomics to evaluate metabolic changes mediated by pro-tumor factors of pancreatic TEMs. Using this model, we have identified CCR1 as a new metabolic regulator of TAMs and CCR1 contributes to the pro-tumor function of TAMs by regulating Arginase 1 expression, a previously identified key immunosuppressive factor in pancreatic cancer. Ultimately, these findings can stimulate future research in targeting CCR1 to enhance anti-tumor immune responses and improve pancreatic cancer patients therapeutic approaches.
