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Theranostics 2022; 12(11):4980-4992. doi:10.7150/thno.73222 This issue Cite

Research Paper

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

Song Han1✉#, Dongtao Fu2#, Gerik W Tushoski1, Lingsong Meng3, Kelly M. Herremans1, Andrea N. Riner1, Thomas J. Geoge4, Zhiguang Huo3, Steven J. Hughes1

1. Department of Surgery, College of Medicine; University of Florida, Gainesville, FL 32610.
2. Department of Pathology, College of Medicine; University of Florida, Gainesville, FL 32610.
3. Department of Biostatistics, College of Medicine; University of Florida, Gainesville, FL 32610.
4. Department of Medicine, College of Medicine; University of Florida, Gainesville, FL 32610.
#These authors contributed equally to this work.

✉ Corresponding author: Song Han, Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL 32610. E-mail: song.hanufl.edu.

Citation:
Han S, Fu D, Tushoski GW, Meng L, Herremans KM, Riner AN, Geoge TJ, Huo Z, Hughes SJ. Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma. Theranostics 2022; 12(11):4980-4992. doi:10.7150/thno.73222. https://www.thno.org/v12p4980.htm
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Abstract

Graphic abstract

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.

Keywords: pancreas, digital spatial profiling, tumor microenvironment, stromal interaction, immune tolerance

Citation styles

APA
Han, S., Fu, D., Tushoski, G.W., Meng, L., Herremans, K.M., Riner, A.N., Geoge, T.J., Huo, Z., Hughes, S.J. (2022). Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma. Theranostics, 12(11), 4980-4992. https://doi.org/10.7150/thno.73222.

ACS
Han, S.; Fu, D.; Tushoski, G.W.; Meng, L.; Herremans, K.M.; Riner, A.N.; Geoge, T.J.; Huo, Z.; Hughes, S.J. Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma. Theranostics 2022, 12 (11), 4980-4992. DOI: 10.7150/thno.73222.

NLM
Han S, Fu D, Tushoski GW, Meng L, Herremans KM, Riner AN, Geoge TJ, Huo Z, Hughes SJ. Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma. Theranostics 2022; 12(11):4980-4992. doi:10.7150/thno.73222. https://www.thno.org/v12p4980.htm

CSE
Han S, Fu D, Tushoski GW, Meng L, Herremans KM, Riner AN, Geoge TJ, Huo Z, Hughes SJ. 2022. Single-cell profiling of microenvironment components by spatial localization in pancreatic ductal adenocarcinoma. Theranostics. 12(11):4980-4992.

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