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

• Published in: Clinical cancer research Vol. 23; no. 17; pp. 5066 - 5073
• Main Authors: Jiang, Ni, Qiao, Guoliang, Wang, Xiaoli, Morse, Michael A, Gwin, William R, Zhou, Lei, Song, Yuguang, Zhao, Yanjie, Chen, Feng, Zhou, Xinna, Huang, Lefu, Hobeika, Amy, Yi, Xin, Xia, Xuefeng, Guan, Yanfang, Song, Jin, Ren, Jun, Lyerly, H Kim
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 01.09.2017
• Subjects: Aged; Cancer; Cancer therapies; CD16 antigen; CD25 antigen; CD28 antigen; CD3 antigen; CD4 antigen; CD56 antigen; CD8 antigen; Chemotherapy; Circulating Tumor DNA - blood; Combined Modality Therapy; Cytokine-Induced Killer Cells - immunology; Cytokines; Dendritic cells; Dendritic Cells - immunology; Deoxyribonucleic acid; Disease-Free Survival; DNA; Drug Combinations; Experimental design; Female; Humans; Immunotherapy; Immunotherapy, Adoptive - adverse effects; Killer cells; Lymphocytes T; Male; Malignancy; Medical treatment; Middle Aged; Mutation; Neoplasm Staging; Oxonic Acid - administration & dosage; Oxonic Acid - adverse effects; Pancreatic cancer; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - pathology; Patients; Peripheral blood; Pyridines - administration & dosage; Pyridines - adverse effects; Risk analysis; Risk factors; Survival; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; Tegafur - administration & dosage; Tegafur - adverse effects; Toxicity
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-17-0492

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. Consecutive patients ( = 47) with advanced pancreatic cancer were treated with either DC-CIK + S-1, DC-CIK alone, S-1 alone, or best supportive care. 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; < 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 ( < 0.05). Phenotypic analysis of PBMCs demonstrated that the CD3 , CD3 /CD4 , and CD8 /CD28 T-cell subsets were elevated ( < 0.05), while the CD3 /CD8 , CD3 /CD16 /CD56 and CD4 /CD25 cell subsets were significantly decreased after DC-CIK cell therapy ( < 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. 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. .