The pathogenesis of treatment failure in patients with Hodgkin lymphoma (HL) treated with chemotherapy is not well understood. Now, a study has shown that a macrophage-like signature in Hodgkin Reed Sternberg cells from patients with HL significantly correlated with treatment failure. Moreover, expression of the CSF1R gene, part of this signature, was significantly associated with progression-free survival and overall survival in 132 patients in an independent validation cohort.