The Role of Complement in Tumor Growth

Overview

Journal Adv Exp Med Biol

Specialties Biology
General Medicine

Date 2013 Nov 26

PMID 24272362

Citations 108

Authors

Ruben Pio

Leticia Corrales

John D Lambris

Affiliations

Soon will be listed here.

Abstract

Complement is a central part of the immune system that has developed as a first defense against non-self cells. Neoplastic transformation is accompanied by an increased capacity of the malignant cells to activate complement. In fact, clinical data demonstrate complement activation in cancer patients. On the basis of the use of protective mechanisms by malignant cells, complement activation has traditionally been considered part of the body's immunosurveillance against cancer. Inhibitory mechanisms of complement activation allow cancer cells to escape from complement-mediated elimination and hamper the clinical efficacy of monoclonal antibody-based cancer immunotherapies. To overcome this limitation, many strategies have been developed with the goal of improving complement-mediated effector mechanisms. However, significant work in recent years has identified new and surprising roles for complement activation within the tumor microenvironment. Recent reports suggest that complement elements can promote tumor growth in the context of chronic inflammation. This chapter reviews the data describing the role of complement activation in cancer immunity, which offers insights that may aid the development of more effective therapeutic approaches to control cancer.

Citing Articles

Proteogenomic Profiling of Treatment-Naïve Metastatic Malignant Melanoma.

Kuras M, Betancourt L, Hong R, Szadai L, Rodriguez J, Horvatovich P Cancers (Basel). 2025; 17(5).

PMID: 40075679 PMC: 11899103. DOI: 10.3390/cancers17050832.

Spatially distinct cellular and molecular landscapes define prognosis in triple negative breast cancer.

Mukund K, Veraksa D, Frankhouser D, Yang L, Tomsic J, Pillai R bioRxiv. 2025; .

PMID: 39990419 PMC: 11844391. DOI: 10.1101/2025.02.10.637503.

The role of the C5a-C5aR pathway in iron metabolism and gastric cancer progression.

Ni Q, Yang H, Rao H, Zhang L, Xiong M, Han X Front Immunol. 2025; 15():1522181.

PMID: 39850877 PMC: 11754390. DOI: 10.3389/fimmu.2024.1522181.

Three-dimensional genome architecture in intrahepatic cholangiocarcinoma.

Liang Y, Li C, Zou R, Ying L, Chen X, Wang Z Cell Oncol (Dordr). 2025; .

PMID: 39831920 DOI: 10.1007/s13402-024-01033-6.

Complement C3d enables cell-mediated immunity capable of distinguishing spontaneously transformed from nontransformed cells.

Platt J, Zhao C, Chicca J, Pianko M, Han J, The S Proc Natl Acad Sci U S A. 2024; 121(52):e2405824121.

PMID: 39693340 PMC: 11670236. DOI: 10.1073/pnas.2405824121.

References

Klickstein L, Barbashov S, Liu T, Jack R, Nicholson-Weller A . Complement receptor type 1 (CR1, CD35) is a receptor for C1q. Immunity. 1997; 7(3):345-55. DOI: 10.1016/s1074-7613(00)80356-8. View

Kolev M, Towner L, Donev R . Complement in cancer and cancer immunotherapy. Arch Immunol Ther Exp (Warsz). 2011; 59(6):407-19. DOI: 10.1007/s00005-011-0146-x. View

Costello L, Franklin R . 'Why do tumour cells glycolyse?': from glycolysis through citrate to lipogenesis. Mol Cell Biochem. 2006; 280(1-2):1-8. PMC: 4461431. DOI: 10.1007/s11010-005-8841-8. View

Schraufstatter I, Trieu K, Sikora L, Sriramarao P, DiScipio R . Complement c3a and c5a induce different signal transduction cascades in endothelial cells. J Immunol. 2002; 169(4):2102-10. DOI: 10.4049/jimmunol.169.4.2102. View

Xu C, Jung M, Burkhardt M, Stephan C, Schnorr D, Loening S . Increased CD59 protein expression predicts a PSA relapse in patients after radical prostatectomy. Prostate. 2004; 62(3):224-32. DOI: 10.1002/pros.20134. View

Okroj M, Hsu Y, Ajona D, Pio R, Blom A . Non-small cell lung cancer cells produce a functional set of complement factor I and its soluble cofactors. Mol Immunol. 2007; 45(1):169-79. DOI: 10.1016/j.molimm.2007.04.025. View

Davis 3rd A, Mejia P, Lu F . Biological activities of C1 inhibitor. Mol Immunol. 2008; 45(16):4057-63. PMC: 2626406. DOI: 10.1016/j.molimm.2008.06.028. View

Blok V, Gelderman K, Tijsma O, Daha M, Gorter A . Cytokines affect resistance of human renal tumour cells to complement-mediated injury. Scand J Immunol. 2003; 57(6):591-9. DOI: 10.1046/j.1365-3083.2003.01265.x. View

Madjd Z, Durrant L, Pinder S, Ellis I, Ronan J, Lewis S . Do poor-prognosis breast tumours express membrane cofactor proteins (CD46)?. Cancer Immunol Immunother. 2004; 54(2):149-56. PMC: 11034299. DOI: 10.1007/s00262-004-0590-0. View

10.

Meri S, Morgan B, Davies A, Daniels R, Olavesen M, Waldmann H . Human protectin (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers. Immunology. 1990; 71(1):1-9. PMC: 1384213. View

11.

Ollert M, David K, Bredehorst R, Vogel C . Classical complement pathway activation on nucleated cells. Role of factor H in the control of deposited C3b. J Immunol. 1995; 155(10):4955-62. View

12.

Reiter Y, Fishelson Z . Targeting of complement to tumor cells by heteroconjugates composed of antibodies and of the complement component C3b. J Immunol. 1989; 142(8):2771-7. View

13.

Badea T, Niculescu F, Soane L, Fosbrink M, Sorana H, Rus V . RGC-32 increases p34CDC2 kinase activity and entry of aortic smooth muscle cells into S-phase. J Biol Chem. 2001; 277(1):502-8. DOI: 10.1074/jbc.M109354200. View

14.

Gminski J, MACHALSKI M, Drozdz M, Najda J . Immunoglobulins and complement components levels in patients with lung cancer. Rom J Intern Med. 1992; 30(1):39-44. View

15.

Liszewski M, Post T, Atkinson J . Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol. 1991; 9:431-55. DOI: 10.1146/annurev.iy.09.040191.002243. View

16.

Podack E, MULLER-EBERHARD H . Isolation of human S-protein, an inhibitor of the membrane attack complex of complement. J Biol Chem. 1979; 254(19):9808-14. View

17.

Mustafa T, Klonisch T, Hombach-Klonisch S, Kehlen A, Schmutzler C, Koehrle J . Expression of CD97 and CD55 in human medullary thyroid carcinomas. Int J Oncol. 2004; 24(2):285-94. View

18.

Kohl J . Anaphylatoxins and infectious and non-infectious inflammatory diseases. Mol Immunol. 2001; 38(2-3):175-87. DOI: 10.1016/s0161-5890(01)00041-4. View

19.

Corey M, Kinders R, Brown L, Vessella R . A very sensitive coupled luminescent assay for cytotoxicity and complement-mediated lysis. J Immunol Methods. 1997; 207(1):43-51. DOI: 10.1016/s0022-1759(97)00098-7. View

20.

Mitchell D, Kirby L, Paulin S, Villiers C, Sim R . Prion protein activates and fixes complement directly via the classical pathway: implications for the mechanism of scrapie agent propagation in lymphoid tissue. Mol Immunol. 2007; 44(11):2997-3004. DOI: 10.1016/j.molimm.2006.12.027. View