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Daugan MV, Revel M, Russick J, et al. Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s. Cancer Immunol Res. 2021;9(8):891-908doi: 10.1158/2326-6066.CIR-20-0532.
Daugan, M. V., Revel, M., Russick, J., Dragon-Durey, M. A., Gaboriaud, C., Robe-Rybkine, T., Poillerat, V., Grunenwald, A., Lacroix, G., Bougouin, A., Meylan, M., Verkarre, V., Oudard, S. M., Mejean, A., Vano, Y. A., Perkins, G., Validire, P., Cathelineau, X., Sanchez-Salas, R., Damotte, D., Fremeaux-Bacchi, V., Cremer, I., Sautès-Fridman, C., Fridman, W. H., & Roumenina, L. T. (2021). Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s. Cancer immunology research, 9(8), 891-908. https://doi.org/10.1158/2326-6066.CIR-20-0532
Daugan, Marie V, et al. "Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s." Cancer immunology research vol. 9,8 (2021): 891-908. doi: https://doi.org/10.1158/2326-6066.CIR-20-0532
Daugan MV, Revel M, Russick J, Dragon-Durey MA, Gaboriaud C, Robe-Rybkine T, Poillerat V, Grunenwald A, Lacroix G, Bougouin A, Meylan M, Verkarre V, Oudard SM, Mejean A, Vano YA, Perkins G, Validire P, Cathelineau X, Sanchez-Salas R, Damotte D, Fremeaux-Bacchi V, Cremer I, Sautès-Fridman C, Fridman WH, Roumenina LT. Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s. Cancer Immunol Res. 2021 Aug;9(8):891-908. doi: 10.1158/2326-6066.CIR-20-0532. Epub 2021 May 26. PMID: 34039653.
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Cancer Immunol Res. 2021 Aug;9(8):891-908. doi: 10.1158/2326-6066.CIR-20-0532. Epub 2021 May 26.

Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s.

Cancer immunology research

Marie V Daugan, Margot Revel, Jules Russick, Marie-Agnès Dragon-Durey, Christine Gaboriaud, Tania Robe-Rybkine, Victoria Poillerat, Anne Grunenwald, Guillaume Lacroix, Antoine Bougouin, Maxime Meylan, Virginie Verkarre, Stephane M Oudard, Arnaud Mejean, Yann A Vano, Geraldine Perkins, Pierre Validire, Xavier Cathelineau, Rafael Sanchez-Salas, Diane Damotte, Veronique Fremeaux-Bacchi, Isabelle Cremer, Catherine Sautès-Fridman, Wolf H Fridman, Lubka T Roumenina

Affiliations

  1. Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.
  2. Université de Paris, Paris, France.
  3. Hôpital Européen Georges-Pompidou, Biological Immunology Department, Assistance Publique Hopitaux de Paris, Paris, France.
  4. University Grenoble Alpes, CNRS, CEA, IBS, Grenoble, France.
  5. Hôpital Européen Georges-Pompidou, Pathology Department, Assistance Publique Hopitaux de Paris, Paris, France.
  6. Hôpital Européen Georges-Pompidou, Oncology Department, Assistance Publique Hopitaux de Paris, Paris, France.
  7. Hôpital Européen Georges-Pompidou, Urology Department, Assistance Publique Hopitaux de Paris, Paris, France.
  8. Hôpital Européen Georges-Pompidou, Gastroenterology and Hepatology Department, Assistance Publique Hopitaux de Paris, Paris, France.
  9. Department of Pathology, Institut Mutualiste Montsouris, Paris, France.
  10. Department of Urology, Institut Mutualiste Montsouris, Paris, France.
  11. Hôpital Cochin, Departments of Pathology and Thoracic Surgery, Assistance Publique Hopitaux de Paris, Paris, France.
  12. Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France. [email protected].

PMID: 34039653 DOI: 10.1158/2326-6066.CIR-20-0532

Abstract

The complement system plays a complex role in cancer. In clear cell renal cell carcinoma (ccRCC), local production of complement proteins drives tumor progression, but the mechanisms by which they do this are poorly understood. We found that complement activation, as reflected by high plasma C4d or as C4d deposits at the tumor site, was associated with poor prognosis in two cohorts of patients with ccRCC. High expression of the C4-activating enzyme C1s by tumor cells was associated with poor prognosis in three cohorts. Multivariate Cox analysis revealed that the prognostic value of C1s was independent from complement deposits, suggesting the possibility of complement cascade-unrelated, protumoral functions for C1s. Silencing of C1s in cancer cell lines resulted in decreased proliferation and viability of the cells and in increased activation of T cells in

©2021 American Association for Cancer Research.

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