Data from Composition, Spatial Characteristics, and Prognostic Significance of Myeloid Cell Infiltration in Pancreatic Cancer
Year: 2023
Type: other
Abstract: Purpose: Although abundant myeloid cell populations in the pancreatic ductal adenocarcinoma (PDAC) microenvironment have been postulated to suppress antitumor immunity, the composition of these populations, their spatial locations, and how they relate to patient outcomes are poorly understood. Experimental Design: To generate spatially resolved tumor and immune cell data at single-cell resolution, we developed two quantitative multiplex immunofluorescence assays to interrogate myeloid cells (CD15, CD14, ARG1, CD33, HLA-DR) and macrophages [CD68, CD163, CD86, IFN regulatory factor 5, MRC1 (CD206)] in the PDAC tumor microenvironment. Spatial point pattern analyses were conducted to assess the degree of colocalization between tumor cells and immune cells. Multivariable-adjusted Cox proportional hazards regression was used to assess associations with patient outcomes. Results: In a multi-institutional cohort of 305 primary PDAC resection specimens, myeloid cells were abundant, enriched within stromal regions, highly heterogeneous across tumors, and differed by somatic genotype. High densities of CD15+ARG1+ immunosuppressive granulocytic cells and M2-polarized macrophages were associated with worse patient survival. Moreover, beyond cell density, closer proximity of M2-polarized macrophages to tumor cells was strongly associated with disease-free survival, revealing the clinical significance and biologic importance of immune cell localization within tumor areas. Conclusions: A diverse set of myeloid cells are present within the PDAC tumor microenvironment and are distributed heterogeneously across patient tumors. Not only the densities but also the spatial locations of myeloid immune cells are associated with patient outcomes, highlighting the potential role of spatially resolved myeloid cell subtypes as quantitative biomarkers for PDAC prognosis and therapy.
Authors: Sara A. Väyrynen, Jinming Zhang, Chen Yuan, Juha P. Väyrynen, Andressa Dias Costa, Hannah Williams, Vicente Morales-Oyarvide, Mai Chan Lau, Douglas A. Rubinson, Richard F. Dunne, Margaret M. Kozak, Wenjia Wang, Diana Agostini-Vulaj, Michael G. Drage, Lauren Brais, Emma Reilly, Osama Rahma, Thomas Clancy, Jiping Wang, David C. Linehan, Andrew J. Aguirre, Charles S. Fuchs, Lisa M. Coussens, Daniel T. Chang, Albert C. Koong, Aram F. Hezel, Shuji Ogino, Jonathan A. Nowak, Brian M. Wolpin
Institutions: Harvard University, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, Brigham and Women's Hospital, University of Rochester Medicine, University of Rochester, Stanford Cancer Institute, Broad Institute, Yale Cancer Center, Yale University, Smilow Cancer Hospital, Oregon Health & Science University, OHSU Knight Cancer Institute, The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4361947166