Abstract A024: B cells facilitate lymph node colonization in pancreatic ductal adenocarcinoma

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate. Several factors contribute to its dismal prognosis, including resistance to available therapies and high invasiveness. Lymph nodes act as an early systemic source of circulating malignant cells in PDAC, allowing their dissemination to other organs early in disease progression. Lymphatic colonization is linked to worse prognosis. Therefore, a better understanding of mechanisms regulating lymph node metastasis is clinically needed. To study each step in the metastatic cascade to the lymph nodes, we have developed a mouse co-clinical model of resectable pancreatic cancer. This model consists of subcutaneous injection of highly metastatic pancreatic cancer cells, followed by surgical resection of the primary tumor. Following resection, mice spontaneously develop lymph nodes metastasis at a comparable frequency to human PDAC post-surgical recurrence, on a similar time scale relative to the lifespans of mice and humans. Expression of nuclear tdTomato allows detection of single cancer cells seeding the draining lymph nodes early in disease progression, even before metastases are histological detectable. Using this model, we are gaining insights into the first steps of metastatic seeding of lymph nodes, and have identified a pro-metastatic role for B cells. These findings will enhance our understanding of lymphatic colonization in PDAC and potentially inform immunotherapeutic interventions to disrupt the metastatic cascade. Citation Format: Alice Bertocchi, Megan T. Hoffman, Li Qiang, Lauren Hsu, Michael Dougan, Judith Agudo, Stephanie K. Dougan. B cells facilitate lymph node colonization in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A024.