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Adaptive Biotechnologies TCRbeta sequencing of 174 primary and 42 metastatic pancreatic ductal adenocarcinoma tumor samples from FFPE curls and 215 matched blood plus 73 additional blood samples

ABSTRACT: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) survive longer if disease spreads to the lung but not the liver. We generated overlapping, multi-omic datasets to identify molecular and cellular features that distinguish patients whose disease develops liver metastasis (liver cohort) from those whose disease develops lung metastasis without liver metastases (lung cohort). Lung cohort patients survived longer than liver cohort patients, despite sharing the same tumor subtype. We developed a pORG gene set enriched in liver cohort versus lung cohort primary tumors. We identified ongoing replication stress (RS) response pathways in high pORG/liver cohort tumors, while low pORG/lung cohort tumors had greater densities of lymphocytes and shared T cell clonal responses. Our study demonstrates that liver-avid PDAC is associated with tolerance to ongoing RS, limited tumor immunity, and less favorable outcomes; whereas low RS, lung-avid/liver-averse tumors are associated with active tumor immunity that may account for favorable outcomes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281005 | GEO | 2024/11/06

REPOSITORIES: GEO

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