High leptin levels independent of body mass index are associated with inflammation and poorer treatment response in patients with diffuse large B-cell lymphoma

Leptin, a protein hormone secreted mainly by adipocytes, plays a key role in modulating various physiological processes. Dysregulation of this hormone has been linked to numerous diseases, including the immunological system and cancer. In patients with diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma (NHL), elevated levels of leptin appear to contribute to the development and progression of lymphoma by modulating the immune system and creating a proinflammatory environment, where lymphoma patients have a lower survival rate compared to those with normal levels. It therefore appears that leptin plays a role in inflammation, the immune system and the development of lymphoma. However, there is a need to fully understand the mechanisms involved and to develop targeted therapies for lymphoma. Our results show that leptin levels are increased (independently of body mass index) in patients with DLBCL belonging to the R2-GDP-GOTEL phase II clinical trial, and these elevated levels are associated with a worse response to treatment and survival using lenalidomide as immunomodulator. Furthermore, a positive correlation between leptin and the inflammation marker C-reactive protein (CRP) is observed, and a multivariate analysis reveals a correlation between leptin, CRP and Monocytic Myeloid-derived suppressor cells (M-MDSC) levels in patients with worse response to treatment. Taken together, these data indicate that leptin could be a promising and predictive response biomarker of treatment efficacy in patients with lymphoma. Our findings on leptin in patients with R/R DLBCL could also arouse great interest given its potential applications as a target of treatment. • Leptin regulates immune and inflammatory processes and is dysregulated in cancer. • High leptin lecels in DLBCL promotes progression and is linked to poorer survival. • In R2-GDP-GOTEL, high leptin (BMI-independent) predicts poor response and survival. • Leptin correlates with CRP and M-MDSCs, markers of inflammation and immune suppression. • Leptin may be a predictive biomarker and therapeutic target in R/R DLBCL.