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Figure S5 from Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

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posted on 2023-04-03, 23:23 authored by 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. Tempero, Robert 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

Figure S5 is related to Figure 5. It shows multiple metrics of intrapatient heterogeneity based on size and histopathology type of assessed tissue.

Funding

Stand Up To Cancer—Lustgarten Foundation Pancreatic Cancer Dream Team Translational Research Grant

National Institutes of Health

National Cancer Institute Human Tumor Atlas Network

NIH

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ARTICLE 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. 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.This article is highlighted in the In This Issue feature, p. 1861

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    Keywords

    BiomarkersPrognostic biomarkersGastrointestinal CancersPancreatic cancerTumor MicroenvironmentImmune cells and the microenvironment

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