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Review
. 2017 Jul 18;15(1):133.
doi: 10.1186/s12916-017-0900-y.

The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome

Deborah R Caswell  1 , Charles Swanton  2   3
Affiliations
Review

The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome

Deborah R Caswell et al. BMC Med. .

Abstract

Background: The advent of rapid and inexpensive sequencing technology allows scientists to decipher heterogeneity within primary tumours, between primary and metastatic sites, and between metastases. Charting the evolutionary history of individual tumours has revealed drivers of tumour heterogeneity and highlighted its impact on therapeutic outcomes.

Discussion: Scientists are using improved sequencing technologies to characterise and address the challenge of tumour heterogeneity, which is a major cause of resistance to therapy and relapse. Heterogeneity may fuel metastasis through the selection of rare, aggressive, somatically altered cells. However, extreme levels of chromosomal instability, which contribute to intratumour heterogeneity, are associated with improved patient outcomes, suggesting a delicate balance between high and low levels of genome instability.

Conclusions: We review evidence that intratumour heterogeneity influences tumour evolution, including metastasis, drug resistance, and the immune response. We discuss the prevalence of tumour heterogeneity, and how it can be initiated and sustained by external and internal forces. Understanding tumour evolution and metastasis could yield novel therapies that leverage the immune system to control emerging tumour neo-antigens.

Keywords: Aneuploidy tolerance; Branched evolution; Competitive evolution; Cooperative evolution; Immunotherapy; Intratumour heterogeneity; Linear evolution; Metastasis; Mutation burden; Tumour progression.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors are both employed at the Francis Crick Institute. Charles Swanton is also a founder of Achilles Therapeutics. Neither author has conflicts of interest related to this article.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The linear progression model versus the parallel progression model of tumour evolution. In the linear progression model (upper panel), late stage tumour cells disseminate and form metastases. In contrast, in the parallel progression model (lower panel), early tumour cells disseminate and form metastases alongside the primary tumour, and both primary tumour and metastases progress in parallel gaining multiple subclonal populations
See this image and copyright information in PMC

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