Abstract B105: Multisite single-cell immune profiling of premetastatic pancreatic ductal adenocarcinoma in a prospective clinical trial
Neha Majety, Ethan S. Agritelley, Elishama N. Kanu, Ashley A. Fletcher, David Severson, Babu Sannareddy, Julia Button, Jiayin Bao, Nicholas Klemen, Peter J. Allen, Daniel Nussbaum, Erika CrosbyAbstract
Background:
Although pancreatic ductal adenocarcinoma (PDAC) has long been considered immunologically "cold," recent studies have revealed complexity in how neoantigen quality, T cell composition, and spatial immune organization influence patient outcomes and responsiveness to emerging immune-based therapies. However, these investigations have largely focused on the primary tumor in isolation, and it remains poorly understood how this integrates with systemic immune responses across the patient and at metastatic sites. We previously developed a multisite immune profiling platform integrating the primary tumor, peripheral blood, and the pre-metastatic liver—the most common site of distant recurrence in PDAC. Here, we applied this platform to a larger panel of patients and healthy donor controls as part of the correlative studies for a prospective clinical trial to more comprehensively understand the coordinated immune landscape of PDAC across multiple tissue compartments.
Methods:
Twenty patients with resectable/borderline resectable PDAC were prospectively enrolled on a clinical trial (NCT05634720) evaluating preoperative hepatic artery infusion chemotherapy. Matched CD45+ immune cells were isolated from the primary tumor, pre-metastatic liver, and peripheral blood, while matched non-immune cells were also collected from the primary tumor. Paired single-cell RNA sequencing and T-cell receptor (TCR) sequencing were performed, with healthy donor peripheral blood samples serving as controls. The study prospectively enrolled two prespecified cohorts: patients undergoing upfront surgery and those receiving three months of neoadjuvant FOLFIRINOX, allowing planned comparisons of systemic chemotherapy-induced changes in immune composition, transcriptional state, and T-cell clonal architecture across all three tissue compartments.
Results/Conclusion:
In total, 1,898,523 immune cells and 98,635 non-immune cells were sequenced from twenty-six patients. Ongoing analysis is focused on defining immune cell composition and transcriptional states across tissue compartments, characterizing T-cell clonal relationships and trafficking between sites, and determining associations between multisite immune features and clinical outcomes, including recurrence and survival. This large dataset provides us with a unique opportunity to expand a previously established multisite immune profiling platform to characterize immune microenvironment cell type composition across tissues, identify tissue-specific differences in patients with early versus late recurrence, and evaluate the effects of systemic chemotherapy on the tumor and surrounding tissue immune microenvironment.
Citation Format:
Neha Majety, Ethan S. Agritelley, Elishama N. Kanu, Ashley A. Fletcher, David Severson, Babu Sannareddy, Julia Button, Jiayin Bao, Nicholas Klemen, Peter J. Allen, Daniel Nussbaum, Erika Crosby. Multisite single-cell immune profiling of premetastatic pancreatic ductal adenocarcinoma in a prospective clinical trial [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr B105.