Anona Brandt
Research Mentor(s): Yaqing Zhang
Mentor Department: Surgery
Authors: Anona Brandt, Faith R. Avritt, Kristee L. Brown, Wei Yan, Yaqing Zhang, Marina Pasca di Magliano
Session: Session 6 (3:00pm – 3:50pm)
Presentation Type: Poster 104
Abstract
Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer with few therapeutic options and no response to immunotherapy. Tumor associated macrophages (TAMs) are one key contributor to the disease’s immunosuppressive microenvironment, prompting its limited treatability. In human and mouse PDA samples, we previously reported a higher expression of the C1q gene in TAMs compared to macrophages from healthy pancreata. The C1q protein complex is a regulator of the complement system, but also a known proliferation agent to tumor cells. We proposed an investigation on the role of C1q in PDA with the hypothesis that its elimination may recruit CD8+ T cells and activate their anti-tumor responses. Utilizing a LysMcre recombinase mouse model, expression of the C1qa subunit was prevented in myeloid cells including macrophages. These C1qa knockout models showed a reduction in tumor mass after PDA orthotopic injection and delayed the formation of Pancreatic Intraepithelial Neoplasia (PanIN) precursor lesions. Further, orthotopic tumors were rescued in their growth when CD8+ T cells were depleted by CD8 blocking antibodies in C1qa KO mice. The decrease in the growth of orthotopic tumors designates C1q targeting as a potential therapeutic approach to defend against pancreatic cancer.
