The Role of the Complement in Clear Cell Renal Carcinoma (ccRCC)-What Future Prospects Are There for Its Use in Clinical Practice?

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Feb 10

PMID 38339243

Authors

Martina Panebianco

Chiara Ciccarese

Alessandro Strusi

Viria Beccia

Carmine Carbone

Antonio Agostini

Geny Piro

Giampaolo Tortora

Roberto Iacovelli

Affiliations

Soon will be listed here.

Abstract

In recent years, the first-line available therapeutic options for metastatic renal cell carcinoma (mRCC) have radically changed with the introduction into clinical practice of new immune checkpoint inhibitor (ICI)-based combinations. Many efforts are focusing on identifying novel prognostic and predictive markers in this setting. The complement system (CS) plays a central role in promoting the growth and progression of mRCC. In particular, mRCC has been defined as an "aggressive complement tumor", which encompasses a group of malignancies with poor prognosie and highly expressed complement components. Several preclinical and retrospective studies have demonstrated the negative prognostic role of the complement in mRCC; however, there is little evidence on its possible role as a predictor of the response to ICIs. The purpose of this review is to explore more deeply the physio-pathological role of the complement in the development of RCC and its possible future use in clinical practice as a prognostic and predictive factor.

Citing Articles

Complement C3 of tumor-derived extracellular vesicles promotes metastasis of RCC via recruitment of immunosuppressive myeloid cells.

Zhang Y, Wang X, Gu Y, Liu T, Zhao X, Cheng S Proc Natl Acad Sci U S A. 2025; 122(4):e2420005122.

PMID: 39847320 PMC: 11789090. DOI: 10.1073/pnas.2420005122.

Clear Cell Renal Cell Carcinoma: A Test Bench for Investigating Tumor Complexity.

Manini C, Lopez-Fernandez E, Larrinaga G, Lopez J Cancers (Basel). 2024; 16(4).

PMID: 38398220 PMC: 10886793. DOI: 10.3390/cancers16040829.

References

Smith M . Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003; 22(47):7359-68. DOI: 10.1038/sj.onc.1206939. View

Markiewski M, DeAngelis R, Benencia F, Ricklin-Lichtsteiner S, Koutoulaki A, Gerard C . Modulation of the antitumor immune response by complement. Nat Immunol. 2008; 9(11):1225-35. PMC: 2678913. DOI: 10.1038/ni.1655. View

ODonnell J, Long G, Scolyer R, Teng M, Smyth M . Resistance to PD1/PDL1 checkpoint inhibition. Cancer Treat Rev. 2016; 52:71-81. DOI: 10.1016/j.ctrv.2016.11.007. View

Ricklin D, Lambris J . Complement-targeted therapeutics. Nat Biotechnol. 2007; 25(11):1265-75. PMC: 2966895. DOI: 10.1038/nbt1342. View

Magrini E, Minute L, Dambra M, Garlanda C . Complement activation in cancer: Effects on tumor-associated myeloid cells and immunosuppression. Semin Immunol. 2022; 60:101642. DOI: 10.1016/j.smim.2022.101642. View

Cho M, Rupaimoole R, Choi H, Noh K, Chen J, Hu Q . Complement Component 3 Is Regulated by TWIST1 and Mediates Epithelial-Mesenchymal Transition. J Immunol. 2016; 196(3):1412-8. PMC: 4724537. DOI: 10.4049/jimmunol.1501886. View

Ricklin D, Lambris J . Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013; 190(8):3831-8. PMC: 3623009. DOI: 10.4049/jimmunol.1203487. View

Nabizadeh J, Manthey H, Steyn F, Chen W, Widiapradja A, Md Akhir F . The Complement C3a Receptor Contributes to Melanoma Tumorigenesis by Inhibiting Neutrophil and CD4+ T Cell Responses. J Immunol. 2016; 196(11):4783-92. DOI: 10.4049/jimmunol.1600210. View

Choueiri T, Powles T, Burotto M, Escudier B, Bourlon M, Zurawski B . Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021; 384(9):829-841. PMC: 8436591. DOI: 10.1056/NEJMoa2026982. View

10.

Xi W, Liu L, Wang J, Xia Y, Bai Q, Long Q . High Level of Anaphylatoxin C5a Predicts Poor Clinical Outcome in Patients with Clear Cell Renal Cell Carcinoma. Sci Rep. 2016; 6:29177. PMC: 4933887. DOI: 10.1038/srep29177. View

11.

Ghebrehiwet B, Silverberg M, Kaplan A . Activation of the classical pathway of complement by Hageman factor fragment. J Exp Med. 1981; 153(3):665-76. PMC: 2186101. DOI: 10.1084/jem.153.3.665. View

12.

Olivieri F, Albertini M, Orciani M, Ceka A, Cricca M, Procopio A . DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging. Oncotarget. 2015; 6(34):35509-21. PMC: 4742121. DOI: 10.18632/oncotarget.5899. View

13.

Gout E, Moriscot C, Doni A, Dumestre-Perard C, Lacroix M, Perard J . M-ficolin interacts with the long pentraxin PTX3: a novel case of cross-talk between soluble pattern-recognition molecules. J Immunol. 2011; 186(10):5815-22. DOI: 10.4049/jimmunol.1100180. View

14.

Albiges L, Tannir N, Burotto M, McDermott D, Plimack E, Barthelemy P . Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open. 2020; 5(6):e001079. PMC: 7703447. DOI: 10.1136/esmoopen-2020-001079. View

15.

Revel M, Sautes-Fridman C, Fridman W, Roumenina L . C1q+ macrophages: passengers or drivers of cancer progression. Trends Cancer. 2022; 8(7):517-526. DOI: 10.1016/j.trecan.2022.02.006. View

16.

Inforzato A, Bottazzi B, Garlanda C, Valentino S, Mantovani A . Pentraxins in humoral innate immunity. Adv Exp Med Biol. 2011; 946:1-20. DOI: 10.1007/978-1-4614-0106-3_1. View

17.

Murakami Y, Imamichi T, Nagasawa S . Characterization of C3a anaphylatoxin receptor on guinea-pig macrophages. Immunology. 1993; 79(4):633-8. PMC: 1421936. View

18.

Hess K, Ajjan R, Phoenix F, Dobo J, Gal P, Schroeder V . Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. PLoS One. 2012; 7(4):e35690. PMC: 3335018. DOI: 10.1371/journal.pone.0035690. View

19.

Motzer R, Alekseev B, Rha S, Porta C, Eto M, Powles T . Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021; 384(14):1289-1300. DOI: 10.1056/NEJMoa2035716. View

20.

Morita T, Kato H, Iwanaga S, Takada K, Kimura T . New fluorogenic substrates for alpha-thrombin, factor Xa, kallikreins, and urokinase. J Biochem. 1977; 82(5):1495-8. DOI: 10.1093/oxfordjournals.jbchem.a131840. View