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The complex dual role of complement on cancer progression

 

Read our review to see how complement activation can promote or hamper cancer progression depending on the tumor type. We propose a novel classification based on a pan-cancer bioinformatics analyses of the expression and prognostic impact of the complement genes in different cancers.  

 

Context-dependent roles of complement in cancer.


Lubka Roumenina, Marie Daugan, Florent Petitprez, Catherine Sautès-Fridman & Wolf Herman Fridman


https://www.nature.com/articles/s41568-019-0210-0

Nat Rev Cancer. 2019 Dec;19(12):698-715. doi: 10.1038/s41568-019-0210-0.

 

The tumour microenvironment (TME) highly influences the growth and spread of tumours, thus impacting the patient's clinical outcome. In this context, the complement system plays a major and complex role. It may either act to kill antibody-coated tumour cells, support local chronic inflammation or hamper antitumour T cell responses favouring tumour progression. Recent studies demonstrate that these opposing effects are dependent upon the sites of complement activation, the composition of the TME and the tumour cell sensitivity to complement attack. In this Review, we present the evidence that has so far accrued showing a role for complement activation and its effects on cancer control and clinical outcome under different TME contexts. We also include a new analysis of the publicly available transcriptomic data to provide an overview of the prognostic value of complement gene expression in 30 cancer types. We argue that the interplay of complement components within each cancer type is unique, governed by the properties of the tumour cells and the TME. This concept is of critical importance for the design of efficient therapeutic strategies aimed at targeting complement components and their signalling.

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