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Single-cell profiling to explore pancreatic cancer heterogeneity, plasticity and response to therapy

Nature Cancer volume 4, pages 454–467 (2023)Cite this article

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer entity characterized by a heterogeneous genetic landscape and an immunosuppressive tumor microenvironment. Recent advances in high-resolution single-cell sequencing and spatial transcriptomics technologies have enabled an in-depth characterization of both malignant and host cell types and increased our understanding of the heterogeneity and plasticity of PDAC in the steady state and under therapeutic perturbation. In this Review we outline single-cell analyses in PDAC, discuss their implications on our understanding of the disease and present future perspectives of multimodal approaches to elucidate its biology and response to therapy at the single-cell level.

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Fig. 1: Single-cell profiling to uncover pancreatic cancer heterogeneity and complexity.
Fig. 2: scRNA-seq approaches to decode cell–cell interaction and communication, as well as the spatial architecture of PDAC subtypes.
Fig. 3: Multimodal spatial single-cell profiling technologies.
Fig. 4: Timeline of subtyping classification advances in pancreatic cancer.

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Acknowledgements

This study was supported by the German Cancer Consortium, Deutsche Forschungsgemeinschaft (DFG SA 1374/8-1 (project ID 515991405), DFG SA 1374/7-1 (project ID 515571394), DGF SCHO 1732/2-1 (project ID 360394750), DFG SA 1374/6-1 (project ID 458890590) and DFG SA 1374/4-3 (project ID 219542602) to D.S. and SFB 1321 (project IDs 329628492 P06, P11 and S01) to R.R. and D.S.), the Wilhelm Sander-Stiftung (2020.174.1 and 2017.091.2 to D.S.) and the European Research Council (ERC CoG No. 648521 to D.S.). C.F. is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute (CRI4641).

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Authors and Affiliations

  1. Division of Translational Cancer Research, German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany

    Stefanie Bärthel, Chiara Falcomatà & Dieter Saur

  2. Institute of Experimental Cancer Therapy, Klinikum Rechts der Isar, School of Medicine, Technische Universität München, Munich, Germany

    Stefanie Bärthel, Chiara Falcomatà & Dieter Saur

  3. Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technische Universität München, Munich, Germany

    Stefanie Bärthel, Chiara Falcomatà, Roland Rad & Dieter Saur

  4. Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Chiara Falcomatà

  5. Institute of Molecular Oncology and Functional Genomics, School of Medicine, Technische Universität München, Munich, Germany

    Roland Rad

  6. German Cancer Consortium Partner Site Munich, Munich, Germany

    Roland Rad

  7. Institute of Computational Biology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany

    Fabian J. Theis

  8. School of Computation, Information and Technology (CIT), Technische Universität München, Munich, Germany

    Fabian J. Theis

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  1. Stefanie Bärthel
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  2. Chiara Falcomatà
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  4. Fabian J. Theis
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  5. Dieter Saur
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Contributions

S.B., C.F., R.R., F.J.T. and D.S. wrote the paper.

Corresponding author

Correspondence to Dieter Saur.

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Competing interests

F.J.T. consults for Immunai Inc., Singularity Bio B.V., CytoReason Ltd, Cellarity and Omniscope Ltd, and has an ownership interest in Dermagnostix GmbH and Cellarity. The other authors declare no competing interests.

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Nature Cancer thanks Arnav Mehta, Nina Steele and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Bärthel, S., Falcomatà, C., Rad, R. et al. Single-cell profiling to explore pancreatic cancer heterogeneity, plasticity and response to therapy. Nat Cancer 4, 454–467 (2023). https://doi.org/10.1038/s43018-023-00526-x

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