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Paracrine promotion of tumor development by the TNF ligand APRIL in Hodgkin's Disease

Leukemia volume 21, pages 1324–1327 (2007)Cite this article

A proliferation-inducing ligand (APRIL) from the tumor necrosis factor (TNF) superfamily co-stimulates B-cell activation. When overexpressed in mice, APRIL induces B-cell neoplasia.1 The promoting activity of APRIL for B-cell derived tumors has been recently reported in vitro for human Hodgkin's lymphoma (HL) cell lines.2 In this work, we sought to ascertain whether APRIL plays a role in the in situ development of HL with a particular emphasis on the pathway(s) involved.

Tumor promotion by host inflammatory reactions is an emerging concept.7 In HL, it is widely accepted that the development of HRS tumor cells is tightly dependent on their interactions with host cells.8 Neutrophils infiltrating HL lesions and secreting APRIL constitute one such interaction that benefits tumor development. The tumor-promoting activity of APRIL highlighted here in situ is unlikely to modulate the primary treatment efficacy of HL. Indeed, failure of initial treatment has become a too rare event8 compared to the number of patients harboring APRIL upregulation. Hence, despite its tumor-promoting activity, APRIL may not constitute an attractive target for the primary treatment of HL. Whether APRIL plays a more relevant role in refractory or relapsed HL cases, which still constitute a clinical burden,8 needs to be further evaluated.

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References

  1. Planelles L, Carvalho-Pinto CE, Hardenberg G, Pals ST, Smaniotto S, Savino W et al. APRIL promotes B-1 cell-associated neoplasm. Cancer Cell 2004; 6: 399–408.

    Article  CAS  Google Scholar 

  2. Chiu A, Xu W, He B, Dillon SR, Gross JA, Sievers E et al. Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL. Blood 2007; 109: 729–739.

    Article  CAS  Google Scholar 

  3. Schwaller J, Schneider P, Mhawech-Fauceglia P, McKee T, Myit S, Matthes T et al. Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B cell lymphoma aggressiveness. Blood 2007; 109: 331–338.

    Article  CAS  Google Scholar 

  4. Ingold K, Zumsteg A, Tardivel A, Huard B, Steiner QG, Cachero TG et al. Identification of proteoglycans as the APRIL-specific binding partners. J Exp Med 2005; 201: 1375–1383.

    Article  CAS  Google Scholar 

  5. Hendriks J, Planelles L, de Jong-Odding J, Hardenberg G, Pals ST, Hahne M et al. Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation. Cell Death Differ 2005; 12: 637–648.

    Article  CAS  Google Scholar 

  6. Bossen C, Ingold K, Tardivel A, Bodmer JL, Gaide O, Hertig S et al. Interactions of tumor necrosis factor (TNF) and TNF receptor family members in the mouse and human. J Biol Chem 2006; 281: 13964–13971.

    Article  CAS  Google Scholar 

  7. Coussens LM, Werb Z . Inflammation and cancer. Nature 2002; 420: 860–867.

    Article  CAS  Google Scholar 

  8. Diehl V, Stein H, Hummel M, Zollinger R, Connors JM . Hodgkin's lymphoma: biology and treatment strategies for primary, refractory, and relapsed disease. Hematology. Am Soc Hematol Educ Program 2003, 225–247.

    Article  Google Scholar 

Download references

Acknowledgements

The technical expertise of Carine Bosshard is greatly acknowledged. This work was supported by the Dinu Lipatti/Henri Dubois-Ferriere foundation. J.S is supported by the Gertrude Von Meissner foundation.

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Authors and Affiliations

  1. Department of Research, University Hospital Basel, Basel, Switzerland

    J Schwaller

  2. Institute of Pathology, University Hospital Basel, Basel, Switzerland

    P Went & S Dirnhofer

  3. Department of Hematology, University Hospital, Geneva, Switzerland

    T Matthes

  4. Apotech Corp., Epalinges, Switzerland

    O Donze

  5. Department of Pathology and Laboratory Medecine, Roswell Park Cancer Institute, Buffalo, NY, USA

    P Mhawech-Fauceglia

  6. Division of Clinical Pathology, University Medical Center, Geneva, Switzerland

    S Myit

  7. Department of Pathology-Immunology, University Medical Center, Geneva, Switzerland

    B Huard

Authors
  1. J Schwaller
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  2. P Went
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  3. T Matthes
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  4. S Dirnhofer
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  5. O Donze
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  6. P Mhawech-Fauceglia
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  7. S Myit
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  8. B Huard
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Corresponding author

Correspondence to B Huard.

Additional information

Competing financial interests: OD is an employee of Apotech Corp. whose reagents have been used in the study. The other authors declare that they have no competing financial interest.

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Schwaller, J., Went, P., Matthes, T. et al. Paracrine promotion of tumor development by the TNF ligand APRIL in Hodgkin's Disease. Leukemia 21, 1324–1327 (2007). https://doi.org/10.1038/sj.leu.2404627

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