Reduced OTUD7B expression correlates with poor prognosis in PTCL via non-canonical NF-κB

Peripheral T cell lymphoma (PTCL) is an aggressive and highly heterogeneous lymphoma with a bleak prognosis, highlighting the urgent need for an effective biomarker to guide therapeutic strategies. Ovarian tumor domain-containing 7B (OTUD7B) has been shown to have a critical function in the progression of cancers. However, the prognostic significance of OTUD7B in PTCL remains unexplored. In this study, we demonstrated for the first time that PTCL patients with low expression of OTUD7B had shorter progression-free survival (PFS) and overall survival (OS). In addition, OTUD7B knockdown promoted chemoresistance to doxorubicin in PTCL cell lines, and led to increased translocation of p52 from the cytoplasm to the nucleus. Inhibition of non-canonical NF-κB partially restored the sensitivity of PTCL cells to doxorubicin. Remarkably, 5-azacytidine and cytarabine upregulated the expression of OTUD7B and exhibited a synergistic anti-lymphoma effect in PTCL. In summary, our study confirmed the prognostic role of OTUD7B in PTCL and the promising therapeutic potential of combining 5-azacytidine or cytarabine and doxorubicin for PTCL treatment.