Complement-induced protection: an explanation for the limitations of cell-based tumour immunotherapies

Kempshall, Emma, Thebault, Simon, Morgan, Bryan Paul ORCID: https://orcid.org/0000-0003-4075-7676, Harris, Claire Louise and Gallimore, Awen Myfanwy ORCID: https://orcid.org/0000-0001-6675-7004 2012. Complement-induced protection: an explanation for the limitations of cell-based tumour immunotherapies. Immunology and Cell Biology 90 (9) , pp. 869-871. 10.1038/icb.2012.30

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Abstract

Complement is involved in the inflammatory response and clearance of infected or altered cells. It is therefore unexpected that complement-deficient animals are less susceptible to carcinogen-induced tumours and more readily control growth of injected tumour cell lines than their wild-type counterparts, implying that complement promotes tumour development and progression. Conversely, natural killer (NK) and CD8+ T cells are known to limit progression of the same tumours. Previous studies indicate that sublytic levels of the complement membrane attack complex protect cells against further attack by lytic doses of complement and other pore-formers such as perforin. We hypothesise that inefficient attack by complement in vivo allows tumour cells to avoid lysis by both NK cells and antigen-specific cytotoxic T cells, thereby promoting tumour outgrowth. Complement could thus be limiting the efficacy of NK and T cell-targeted cancer therapies, and the inclusion of complement inhibitors could optimise these immunotherapeutic regimes.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	complement, induced protection, MAC, immunotherapy, NK, CD8+ T cell, tumour
Publisher:	Nature Publishing Group
ISSN:	0818-9641
Last Modified:	21 Oct 2022 10:49
URI:	https://orca.cardiff.ac.uk/id/eprint/41444

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