Complement-induced protection: an explanation for the limitations of cell-based tumour immunotherapies.
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.
The Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK. Kempshallec1@cardiff.ac.uk
Emma
E
Kempshall
Simon
S
Thebault
B Paul
BP
Morgan
Claire L
CL
Harris
Awen
A
Gallimore
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D054353:Perforin / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
D015938:Complement Membrane Attack Complex; D054353:Perforin; D003165:Complement System Proteins