Primary refractory and early-relapsed Hodgkin's lymphoma: Strategies for therapeutic targeting based on the tumour microenvironment

Antonino Carbone, Annunziata Gloghini, Luca Castagna, Armando Santoro, Carmelo Carlo-Stella

Research output: Contribution to journalArticlepeer-review


Classical Hodgkin's lymphoma (cHL), a distinct disease entity with characteristic clinical and pathological features, accounts for approximately 10% of all malignant lymphomas. cHL can be considered a prototype model for how the tumour microenvironment influences cancer pathogenesis. Cellular components of the cHL microenvironment express molecules involved in cancer cell growth and survival, such as CD30L or CD40L. Moreover, several signal transduction pathways that are critical for the proliferation and survival of neoplastic Hodgkin Reed-Sternberg (HRS) cells, including NF-κB, JAK-STAT, PI3K-AkT and ERK, are deregulated in cHL. Although most patients can be cured with modern treatment strategies, approximately a quarter experience either primary or secondary chemorefractoriness or disease relapse, thus requiring novel treatments. Preclinical and clinical evidence has elucidated a complex crosstalk between malignant HRS cells and the reactive cells of the microenvironment, which suggests that novel therapeutic approaches capable of targeting HRS cells along with reactive cells might overcome chemorefractoriness. In the near future, these novel therapies will also be tested in chemosensitive patients, to reduce the long-term toxicity of chemo-radiotherapy.

Original languageEnglish
Pages (from-to)4-13
Number of pages10
JournalJournal of Pathology
Issue number1
Publication statusPublished - Sep 1 2015


  • chemorefractoriness
  • early-relapsed Hodgkin's lymphoma
  • Hodgkin Reed-Sternberg cells
  • Hodgkin's lymphoma
  • Hodgkin's lymphoma microenvironment
  • microenvironment
  • refractory Hodgkin's lymphoma
  • signalling pathways
  • transcription factors
  • tumour microenvironment

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)


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