Dendritic Cell/Cytokine-Induced Killer Cell Immunotherapy Combined with S-1 in Patients with Advanced Pancreatic Cancer: A Prospective Study.

Abstract

<b>Purpose:</b> Advanced pancreatic cancer has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells (DC-CIK) administered with the chemotherapy (CT) S-1 in this malignancy.<b>Experimental Design:</b> Consecutive patients (<i>n</i> = 47) with advanced pancreatic cancer were treated with either DC-CIK + S-1, DC-CIK alone, S-1 alone, or best supportive care.<b>Results:</b> DC-CIK plus S-1 produced significantly longer median OS and PFS (212 and 136 days) compared with DC-CIK (128 and 85 days), CT (141 and 92 days), or supportive care only (52 and 43 days; <i>P</i> < 0.001). After adjusting for competing risk factors, DC-CIK combined with S-1 and receipt of 2 or more cycles of DC-CIK treatment remained independent predictors of disease-free and overall survival (<i>P</i> < 0.05). Phenotypic analysis of PBMCs demonstrated that the CD3⁺, CD3⁺/CD4⁺, and CD8⁺/CD28⁺ T-cell subsets were elevated (<i>P</i> < 0.05), while the CD3⁺/CD8⁺, CD3⁺/CD16⁺/CD56⁺ and CD4⁺/CD25⁺ cell subsets were significantly decreased after DC-CIK cell therapy (<i>P</i> < 0.05). There were no grade 3 or 4 toxicities. In addition, the mutational frequency in cell-free tumor DNA (cfDNA) declined in 4 of 14 patients who received DC-CIK, and was associated with a more favorable survival.<b>Conclusions:</b> Treatment of advanced pancreatic cancer with combined DC-CIK infusions and S-1 was safe, resulted in favorable PFS and OS, and modulated the peripheral blood immune repertoire. <i>Clin Cancer Res; 23(17); 5066-73. ©2017 AACR</i>.