Journal
CANCER DISCOVERY
Volume 11, Issue 8, Pages 2014-2031Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-20-0841
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Funding
- Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Dream Team Translational Research Grant [SU2C-AACR-DT14-14]
- Brenden-Colson Center for Pancreatic Care at OHSU
- National Institutes of Health [1U01 CA224012, U2C CA233280, R01 CA223150, R01 CA226909, R21 HD099367, U01 CA210171, P50 CA127003, U54 CA209988, R01 CA196228, R01 CA186241]
- Knight Cancer Institute
- National Institutes of Health, National Cancer Institute Human Tumor Atlas Network (HTAN) Research Center [U2C CA233280]
- Prospect Creek Foundation
- Hale Family Center for Pancreatic Cancer Research
- Lustgarten Foundation Dedicated Laboratory program
- Stand Up To Cancer
- Pancreatic Cancer Action Network
- Noble Effort Fund
- Wexler Family Fund
- Promises for Purple
- McCarthy Strong
- Finnish Cultural Foundation
- Orion Research Foundation
- Apexigen
- Fibrogen
- Inovio
- Janssen
- Lilly
- Oregon Clinical & Translational Research Institute (OCTRI) - National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR002369]
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Researchers have established an immune atlas of PDAC through single-cell resolution profiling, identifying leukocyte features correlated with clinical outcomes, which can serve as a valuable reference for PDAC treatment. The data can aid in deeper understanding of the PDAC immune ecosystem, identifying additional therapeutic targets, and providing predictive biomarkers for therapeutic response and resistance monitoring.
Immunotherapies targeting aspects of T cell functionality are efficacious in many solid tumors, but pancreatic ductal adenocarcinoma (PDAC) remains refractory to these treatments. Deeper understanding of the PDAC immune ecosystem is needed to identify additional therapeutic targets and predictive biomarkers for therapeutic response and resistance monitoring. To address these needs, we quantitatively evaluated leukocyte contexture in 135 human PDACs at single-cell resolution by profiling density and spatial distribution of myeloid and lymphoid cells within histopathologically defined regions of surgical resections from treatment-naive and presurgically (neoadjuvant)-treated patients and biopsy specimens from metastatic PDAC. Resultant data establish an immune atlas of PDAC heterogeneity, identify leukocyte features correlating with clinical outcomes, and, through an in silico study, provide guidance for use of PDAC tissue microarrays to optimally measure intratumoral immune heterogeneity. Atlas data have direct applicability as a reference for evaluating immune responses to investigational neoadjuvant PDAC therapeutics where pretherapy baseline specimens are not available. SIGNIFICANCE: We provide a phenotypic and spatial immune atlas of human PDAC identifying leukocyte composition at steady state and following standard neoadjuvant therapies. These data have broad utility as a resource that can inform on leukocyte responses to emerging therapies where baseline tissues were not acquired.
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