Leukocyte heterogeneity in pancreatic ductal adenocarcinoma: Phenotypic and spatial features associated with clinical outcome

Shannon M. Liudahl, Courtney B. Betts, Shamilene Sivagnanam, Vicente Morales-Oyarvide, Annacarolina Da Silva, Chen Yuan, Samuel Hwang, Alison Grossblatt-Wait, Kenna R. Leis, William Larson, Meghan B. Lavoie, Padraic Robinson, Andressa Dias Costa, Sara A. Väyrynen, Thomas E. Clancy, Douglas A. Rubinson, Jason Link, Dove Keith, Wesley Horton, Margaret A. TemperoRobert H. Vonderheide, Elizabeth M. Jaffee, Brett Sheppard, Jeremy Goecks, Rosalie C. Sears, Byung S. Park, Motomi Mori, Jonathan A. Nowak, Brian M. Wolpin, Lisa M. Coussens

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2014-2031
Number of pages18
JournalCancer discovery
Volume11
Issue number8
DOIs
StatePublished - Aug 2021

ASJC Scopus subject areas

  • Oncology

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