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Cancer-associated fibroblasts in the single-cell era

Nature Cancer volume 3, pages 793–807 (2022)Cite this article

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Abstract

Cancer-associated fibroblasts (CAFs) are central players in the microenvironment of solid tumors, affecting cancer progression and metastasis. CAFs have diverse phenotypes, origins and functions and consist of distinct subpopulations. Recent progress in single-cell RNA-sequencing technologies has enabled detailed characterization of the complexity and heterogeneity of CAF subpopulations in multiple tumor types. In this Review, we discuss the current understanding of CAF subsets and functions as elucidated by single-cell technologies, their functional plasticity, and their emergent shared and organ-specific features that could potentially be harnessed to design better therapeutic strategies for cancer.

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Fig. 1: Primary CAF subsets and their potential origins.
Fig. 2: Identification of discrete CAF subsets achieved through different experimental systems.
Fig. 3: scRNA-seq reveals multiple tasks undertaken by discrete CAF subtypes.
Fig. 4: scRNA-seq analyses reveal universal as well as organ-specific CAF subsets.
Fig. 5: Examples of potential CAF targeting.

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Acknowledgements

A.B.-S. is supported by the Israel Cancer Research Fund (ICRF). N.E. is supported by the Department of Defense, Worldwide Cancer Research, the Israel Science Foundation and the ICRF. R.S.-S. is supported by the Israel Science Foundation, ERC starting grant 754320, the ICRF, the Laura Gurwin Flug Family Fund and the estate of David Levinson. R.S.-S. is the incumbent of the Ernst and Kaethe Ascher Career Development Chair in Life Sciences.

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  1. These authors contributed equally: Dor Lavie, Aviad Ben-Shmuel.

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  1. Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Dor Lavie & Neta Erez

  2. Department of Biomolecular Sciences, the Weizmann Institute of Science, Rehovot, Israel

    Aviad Ben-Shmuel & Ruth Scherz-Shouval

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Lavie, D., Ben-Shmuel, A., Erez, N. et al. Cancer-associated fibroblasts in the single-cell era. Nat Cancer 3, 793–807 (2022). https://doi.org/10.1038/s43018-022-00411-z

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