Adoptive transfer of natural killer cells in combination with chemotherapy improves outcomes of patients with locally advanced colon carcinoma

Abstract

BackgroundDespite the availability of multiple treatment strategies, patients with advanced colon carcinoma (CC) have poor prognoses. The aim of this study was to evaluate the efficacy and safety of natural killer (NK) cell therapy in combination with chemotherapy in patients with locally advanced CC. MethodsWe assessed the cytotoxicity of NK cells to CC cells (CCs) and CC stem cells (CSCs) pre-treated with 5-fluorouracil or oxaliplatin in vitro. Then, an open-label cohort study was conducted with locally advanced CC patients who had received radical resection. Patients received either NK cell therapy combined with chemotherapy (NK cell group, 27 patients) or pure chemotherapy (control group, 33 patients). Progression-free survival (PFS), overall survival (OS) and adverse effects were investigated. ResultsChemotherapy sensitized CCs and CSCs to NK cell cytotoxicity through regulation of NK cell–activating/inhibitory receptor ligands. Poorly differentiated CCs were more susceptible to NK cells than well-differentiated ones. In the cohort study, the 5-year PFS and OS rates in the NK cell group were significantly higher than those in the control group (51.1% versus 35%, P = 0.044; 72.5% versus 51.6%, P = 0.037, respectively). Among patients with poorly differentiated carcinomas and low expression of human leukocyte antigen (HLA)-1, the median PFS in the NK cell group versus the control group was 23.5 versus 12.1 months (P = 0.0475) and 33.1 versus 18.5 months (P = 0.045), respectively. No significant adverse reactions were reported. ConclusionNK cell therapy in combination with chemotherapy in locally advanced CC prevented recurrence and prolonged survival with acceptable adverse effects, especially for poorly differentiated carcinomas.