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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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.
The authors declare no competing interests.
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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