Cargando…

Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma

Rationale: The biology of the pancreatic ductal adenocarcinoma (PDAC) is heterogenous, but how heterogenity of the tumor microenvironment contributes to disparate patient outcomes remains essentially unstudied. Methods: A strategy employing multiplex digital spatial profiling (mplxDSP) technology wa...

Descripción completa

Detalles Bibliográficos
Autores principales: Han, Song, Fu, Dongtao, Tushoski, Gerik W, Meng, Lingsong, Herremans, Kelly M., Riner, Andrea N., Geoge, Thomas J., Huo, Zhiguang, Hughes, Steven J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274743/
https://www.ncbi.nlm.nih.gov/pubmed/35836806
http://dx.doi.org/10.7150/thno.73222
_version_ 1784745353705160704
author Han, Song
Fu, Dongtao
Tushoski, Gerik W
Meng, Lingsong
Herremans, Kelly M.
Riner, Andrea N.
Geoge, Thomas J.
Huo, Zhiguang
Hughes, Steven J.
author_facet Han, Song
Fu, Dongtao
Tushoski, Gerik W
Meng, Lingsong
Herremans, Kelly M.
Riner, Andrea N.
Geoge, Thomas J.
Huo, Zhiguang
Hughes, Steven J.
author_sort Han, Song
collection PubMed
description Rationale: The biology of the pancreatic ductal adenocarcinoma (PDAC) is heterogenous, but how heterogenity of the tumor microenvironment contributes to disparate patient outcomes remains essentially unstudied. Methods: A strategy employing multiplex digital spatial profiling (mplxDSP) technology was employed to evaluate the nature and dynamics of microenvironment components including cancer associated fibroblasts (CAFs) and infiltrating immune cells at the single-cell level based upon their spatial relationship within the tumor. Results: We report that myofibroblasts directly adjacent to PDAC tumors comparatively overexpress genes (BATF3, IL12B, ITGB8, CD4 and IFNAR1), constructing pathways prone to stimulating an adaptive immune response. Markers of innate immune cells (Natural Killer cells, Dendritic Cells and macrophages) are predominant in CD45+ cells immediately adjacent to PDAC tumor, however, the checkpoint protein CTLA4 is also overwhelmingly expressed, fostering tolerance. Finaly, mRNA profiling of adjacent CAFs identified clusters of genes that correlate with survival. Conclusion: CAFs and leukocytes in close proximity to PDAC significantly differ from those remote from the tumor, providing insight into microenvironment influence on immune tolerance mediated through relative populations of leukocytes and subsets of CAFs and monocytes. mRNA expression profiling of CAFs adjacent to PDAC cells may hold promise for prognostication.
format Online
Article
Text
id pubmed-9274743
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-92747432022-07-13 Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma Han, Song Fu, Dongtao Tushoski, Gerik W Meng, Lingsong Herremans, Kelly M. Riner, Andrea N. Geoge, Thomas J. Huo, Zhiguang Hughes, Steven J. Theranostics Research Paper Rationale: The biology of the pancreatic ductal adenocarcinoma (PDAC) is heterogenous, but how heterogenity of the tumor microenvironment contributes to disparate patient outcomes remains essentially unstudied. Methods: A strategy employing multiplex digital spatial profiling (mplxDSP) technology was employed to evaluate the nature and dynamics of microenvironment components including cancer associated fibroblasts (CAFs) and infiltrating immune cells at the single-cell level based upon their spatial relationship within the tumor. Results: We report that myofibroblasts directly adjacent to PDAC tumors comparatively overexpress genes (BATF3, IL12B, ITGB8, CD4 and IFNAR1), constructing pathways prone to stimulating an adaptive immune response. Markers of innate immune cells (Natural Killer cells, Dendritic Cells and macrophages) are predominant in CD45+ cells immediately adjacent to PDAC tumor, however, the checkpoint protein CTLA4 is also overwhelmingly expressed, fostering tolerance. Finaly, mRNA profiling of adjacent CAFs identified clusters of genes that correlate with survival. Conclusion: CAFs and leukocytes in close proximity to PDAC significantly differ from those remote from the tumor, providing insight into microenvironment influence on immune tolerance mediated through relative populations of leukocytes and subsets of CAFs and monocytes. mRNA expression profiling of CAFs adjacent to PDAC cells may hold promise for prognostication. Ivyspring International Publisher 2022-06-27 /pmc/articles/PMC9274743/ /pubmed/35836806 http://dx.doi.org/10.7150/thno.73222 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Han, Song
Fu, Dongtao
Tushoski, Gerik W
Meng, Lingsong
Herremans, Kelly M.
Riner, Andrea N.
Geoge, Thomas J.
Huo, Zhiguang
Hughes, Steven J.
Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma
title Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma
title_full Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma
title_fullStr Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma
title_full_unstemmed Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma
title_short Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma
title_sort single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274743/
https://www.ncbi.nlm.nih.gov/pubmed/35836806
http://dx.doi.org/10.7150/thno.73222
work_keys_str_mv AT hansong singlecellprofilingofmicroenvironmentcomponentsbyspatiallocalizationinpancreaticductaladenocarcinoma
AT fudongtao singlecellprofilingofmicroenvironmentcomponentsbyspatiallocalizationinpancreaticductaladenocarcinoma
AT tushoskigerikw singlecellprofilingofmicroenvironmentcomponentsbyspatiallocalizationinpancreaticductaladenocarcinoma
AT menglingsong singlecellprofilingofmicroenvironmentcomponentsbyspatiallocalizationinpancreaticductaladenocarcinoma
AT herremanskellym singlecellprofilingofmicroenvironmentcomponentsbyspatiallocalizationinpancreaticductaladenocarcinoma
AT rinerandrean singlecellprofilingofmicroenvironmentcomponentsbyspatiallocalizationinpancreaticductaladenocarcinoma
AT geogethomasj singlecellprofilingofmicroenvironmentcomponentsbyspatiallocalizationinpancreaticductaladenocarcinoma
AT huozhiguang singlecellprofilingofmicroenvironmentcomponentsbyspatiallocalizationinpancreaticductaladenocarcinoma
AT hughesstevenj singlecellprofilingofmicroenvironmentcomponentsbyspatiallocalizationinpancreaticductaladenocarcinoma