Defining and using immune archetypes to classify and treat cancer

Alexis J Combes; Bushra Samad; Matthew F Krummel

doi:10.1038/s41568-023-00578-2

Defining and using immune archetypes to classify and treat cancer

Nat Rev Cancer. 2023 Jul;23(7):491-505. doi: 10.1038/s41568-023-00578-2. Epub 2023 Jun 5.

Authors

Alexis J Combes^{1

2

3

4

5}, Bushra Samad^{6

7

8

9}, Matthew F Krummel^{10

11

12}

Affiliations

¹ Department of Pathology, University of California San Francisco, San Francisco, CA, USA. alexis.combes@ucsf.edu.
² Bakar ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA. alexis.combes@ucsf.edu.
³ UCSF Immunoprofiler Initiative, University of California San Francisco, San Francisco, CA, USA. alexis.combes@ucsf.edu.
⁴ UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA. alexis.combes@ucsf.edu.
⁵ Department of Medicine, University of California San Francisco, San Francisco, CA, USA. alexis.combes@ucsf.edu.
⁶ Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
⁷ Bakar ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
⁸ UCSF Immunoprofiler Initiative, University of California San Francisco, San Francisco, CA, USA.
⁹ UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Department of Pathology, University of California San Francisco, San Francisco, CA, USA. matthew.krummel@ucsf.edu.
¹¹ Bakar ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA. matthew.krummel@ucsf.edu.
¹² UCSF Immunoprofiler Initiative, University of California San Francisco, San Francisco, CA, USA. matthew.krummel@ucsf.edu.

PMID: 37277485
DOI: 10.1038/s41568-023-00578-2

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.

Publication types

Review

MeSH terms

Humans
Neoplasms* / drug therapy
Neoplasms* / therapy
Tumor Microenvironment