Classical Hodgkin lymphoma cells may promote an IL-17-enriched microenvironment

Abstract

In classical Hodgkin lymphoma (cHL), the significance of the interplay between Hodgkin and Reed–Sternberg cells (HRS) and reactive T cells remains poorly defined. By immunohistochemistry on bioptic cHL specimens, we found that HRS and surrounding T lymphocytes stained positive for IL-17 in 40% of cases. IL-17 was detectable in a similar proportion of patients’ sera and correlated with disease burden. Supernatants of KM-H2 and HDLM-2 cHL cell lines guided preferential chemotaxis of CCR6⁺ T lymphocytes. Coculture of cHL cell lines with PBMC promoted the enrichment of Th17 lymphocytes and Foxp3⁺/IL-17⁺ cells, whereas T regulatory cells slightly decreased. Soluble CD30 downmodulated membrane CD30 expression on T cells and contributed to their polarization shift by stimulating IL-17 production and reducing IFN-γ synthesis. Thus, HRS and a number of reactive CD4⁺ T cells, attracted by tumor-secreted chemokines, produce an IL-17 tumor-shaped inflammatory milieu in a cHL subset.

Keywords:

• Interleukin 17
• classical Hodgkin lymphoma
• microenvironment
• T helper lymphocytes
• CD30

Disclosure statement

The authors declare no competing financial interests.

Additional information

Funding

This work was supported by Italian Association for Cancer Research (AIRC, Milan, Italy)/Cariverona Foundation (Verona, Italy). FV wants to express his gratitude to Maria Langhieri for supporting cancer research in memory of her mother Iliana Tescaroli.