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Defining and using immune archetypes to classify and treat cancer

Nature Reviews Cancer volume 23, pages 491–505 (2023)Cite this article

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Abstract

Tumours are surrounded by a host immune system that can suppress or promote tumour growth. The tumour microenvironment (TME) has often been framed as a singular entity, suggesting a single type of immune state that is defective and in need of therapeutic intervention. By contrast, the past few years have highlighted a plurality of immune states that can surround tumours. In this Perspective, we suggest that different TMEs have ‘archetypal’ qualities across all cancers — characteristic and repeating collections of cells and gene-expression profiles at the level of the bulk tumour. We discuss many studies that together support a view that tumours typically draw from a finite number (around 12) of ‘dominant’ immune archetypes. In considering the likely evolutionary origin and roles of these archetypes, their associated TMEs can be predicted to have specific vulnerabilities that can be leveraged as targets for cancer treatment with expected and addressable adverse effects for patients.

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Fig. 1: The yin and yang of dominant and reactive archetypes.
Fig. 2: Pan-cancer census of TMEs across solid tumours.
Fig. 3: Tissue distribution and potential ‘distance’ between dominant immune archetypes.
Fig. 4: The dominant tumour immune archetype is associated with different disease outcomes in patients with kidney cancer.
Fig. 5: The dominant tumour-promoting immune archetype serves as a scaffold to identify the reactive tumour-eliminating cellular network.

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Acknowledgements

The authors thank K. Hu and T. Courau for proofreading the manuscript and members of the Krummel laboratory and ImmunoX for discussions and shared insights.

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Authors and Affiliations

  1. Department of Pathology, University of California San Francisco, San Francisco, CA, USA

    Alexis J. Combes, Bushra Samad & Matthew F. Krummel

  2. Bakar ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA

    Alexis J. Combes, Bushra Samad & Matthew F. Krummel

  3. UCSF Immunoprofiler Initiative, University of California San Francisco, San Francisco, CA, USA

    Alexis J. Combes, Bushra Samad & Matthew F. Krummel

  4. UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA

    Alexis J. Combes & Bushra Samad

  5. Department of Medicine, University of California San Francisco, San Francisco, CA, USA

    Alexis J. Combes

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M.F.K. made a substantial contribution to discussion of content, wrote and reviewed/edited the manuscript before submission. A.J.C. researched data for the article, made a substantial contribution to discussion of content, wrote and reviewed/edited the manuscript before submission. B.S. researched data for the article, made a substantial contribution to discussion of content and reviewed/edited the manuscript before submission.

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Correspondence to Alexis J. Combes or Matthew F. Krummel.

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Combes, A.J., Samad, B. & Krummel, M.F. Defining and using immune archetypes to classify and treat cancer. Nat Rev Cancer 23, 491–505 (2023). https://doi.org/10.1038/s41568-023-00578-2

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