TY - JOUR
T1 - Leukocyte heterogeneity in pancreatic ductal adenocarcinoma
T2 - Phenotypic and spatial features associated with clinical outcome
AU - Liudahl, Shannon M.
AU - Betts, Courtney B.
AU - Sivagnanam, Shamilene
AU - Morales-Oyarvide, Vicente
AU - Silva, Annacarolina Da
AU - Yuan, Chen
AU - Hwang, Samuel
AU - Grossblatt-Wait, Alison
AU - Leis, Kenna R.
AU - Larson, William
AU - Lavoie, Meghan B.
AU - Robinson, Padraic
AU - Costa, Andressa Dias
AU - Väyrynen, Sara A.
AU - Clancy, Thomas E.
AU - Rubinson, Douglas A.
AU - Link, Jason
AU - Keith, Dove
AU - Horton, Wesley
AU - Tempero, Margaret A.
AU - Vonderheide, Robert H.
AU - Jaffee, Elizabeth M.
AU - Sheppard, Brett
AU - Goecks, Jeremy
AU - Sears, Rosalie C.
AU - Park, Byung S.
AU - Mori, Motomi
AU - Nowak, Jonathan A.
AU - Wolpin, Brian M.
AU - Coussens, Lisa M.
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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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U2 - 10.1158/2159-8290.CD-20-0841
DO - 10.1158/2159-8290.CD-20-0841
M3 - Article
C2 - 33727309
AN - SCOPUS:85107469167
SN - 2159-8274
VL - 11
SP - 2014
EP - 2031
JO - Cancer discovery
JF - Cancer discovery
IS - 8
ER -