Inflammatory cytokine-associated cisplatin resistance in non-small cell lung cancer and re-sensitization through interleukin-6 receptor blockade

Chemoresistance remains a major challenge in non-small cell lung cancer, especially for cisplatin (DDP)-based therapies, which are a mainstay of treatment. In their study, Dai <i>et al</i> investigate how inflammatory cytokines within the tumor microenvironment contribute to DDP resistance. By analyzing tumor samples from 20 non-small cell lung cancer patients and two resistant cell lines (A549/ DDP and SK-MES-1/DDP), the authors show that increased levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α are linked to resistance. Logistic regression identifies IL-6 and IL-8 as key risk factors. Functional experiments using tocilizumab, an IL-6 receptor antagonist, demonstrate a reduction in DDP half maximum inhibitory concentration, higher apoptosis rates, and decreased migration and invasion in resistant cells. Although the study has certain limitations, such as the analysis of only five inflammatory cytokines in a small, non-stratified patient cohort; it demonstrates that targeting the IL-6 cytokine axis may help overcome DDP resistance. Overall, the study highlights the inflammatory component of the tumor microenvironment as a modifiable driver of chemoresistance and provide a rationale for integrating cytokine blockade into platinum-based chemotherapy regimens to enhance therapeutic response.