Synergistic antitumor efficacy of CIK cells combined with PD-1 inhibitors in nasopharyngeal carcinoma.

OBJECTIVES: To investigate the synergistic anti-tumor effects and underlying mechanisms of combining cytokine-induced killer (CIK) cell therapy with programmed death 1 (PD-1) blockade in the treatment of nasopharyngeal carcinoma (NPC). METHODS: CIK cells were generated from peripheral blood mononuclear cells (PBMCs) of healthy donors. The combinatorial effects were assessed in vitro by co-culturing CIK cells with HK-1 NPC cells to assess cytotoxicity, apoptosis-related gene expression, cytokine secretion, and activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. In vivo efficacy was evaluated in a NOD scid gamma (NSG) mouse xenograft model (n=6/group). RESULTS: In vitro, PD-1 blockade dose-dependently enhanced CIK cell-mediated cytotoxicity, apoptosis, and secretion of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2), concomitant with MEK/ERK pathway activation. In vivo, combination therapy significantly inhibited tumor growth compared with either monotherapy. This was associated with increased infiltration of cluster of differentiation (CD)3(+), CD4(+), CD8(+), and CD56(+) immune cells, enhanced tumor apoptosis (TUNEL+), reduced proliferation (Ki67), and alleviated oxidative stress within the tumor microenvironment. CONCLUSIONS: Combined CIK cell therapy and PD-1 blockade demonstrated significant synergistic anti-tumor activity against NPC by enhancing cytotoxicity, activating key signaling pathways, and remodeling the tumor immune microenvironment. This strategy represents a promising therapeutic approach for NPC.