Abstract
Adoptive immunotherapy using cytokine-induced killer (CIK) cells is a promising cancer treatment, but its efficacy is restricted by various factors, including the accumulation of myeloid-derived suppressor cells (MDSCs). In this study, we determine whether chemotherapeutic drugs that reduce MDSC levels enhance the efficacy of CIK cell therapy in the treatment of solid tumors. Fifty-three patients were included in this study; 17 were diagnosed with metastatic renal cell carcinoma (MRCC), 10 with advanced pancreatic cancer (PC), and 26 with metastatic melanoma (MM). These patients were divided into two groups: CIK cell therapy alone and CIK cell therapy combined with chemotherapy. Combining CIK cell therapy and chemotherapy increased 1-year survival rates and median survival times in MRCC and PC patients, but not in MM patients. The disease control rate did not differ between treatment groups for MRCC or MM patients, but was higher in PC patients receiving combined treatment than CIK cell treatment alone. These data suggest that addition of MDSC-decreasing chemotherapy to CIK cell therapy improves survival in MRCC and PC patients.
Highlights
Surgical intervention after an early diagnosis is highly effective, the prognoses for metastatic renal cell carcinoma (MRCC), metastatic melanoma (MM), and pancreatic cancer (PC) remain poor
Our results suggest that combining chemotherapy with immunotherapy might improve survival in MRCC and PC patients
It was reported that combining gemcitabine and/or S-1 chemotherapy with dendritic cell vaccine immunotherapy prolongs median survival to 12 months [30], while the median survival was 8.8– 10.1 months when these chemotherapy drugs were not combined with the immunotherapy (31)
Summary
Surgical intervention after an early diagnosis is highly effective, the prognoses for metastatic renal cell carcinoma (MRCC), metastatic melanoma (MM), and pancreatic cancer (PC) remain poor. The median survival time of MRCC patients is 10 months [1], and the 5-year survival rate is less than 10% [2]. For MM patients, the median survival time is 8 to 9 months, and the 3-year survival rate is less than 15% [3]. The development of new therapies, including VEGF axis inhibitors for MRCC and a BRAF inhibitor for MM, has helped improve survival rates in advanced patients. These drugs rarely induce a complete and enduring response. Checkpoint inhibitors, such as monoclonal antibodies against cytotoxic T-lymphocyteassociated antigen 4 and programmed death 1, represent a breakthrough in the treatment of solid tumors, including
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