Clinical effects of autologous dendritic cells combined with cytokine-induced killer cells followed by chemotherapy in treating patients with advanced colorectal cancer: a prospective study

Abstract

The objective of this study was to evaluate the effects of dendritic cell and cytokine-induced killer (DC-CIK) cell-based immunotherapy combined with chemotherapy on the treatment of patients with advanced colorectal cancer. We prospectively included patients with advanced colorectal cancer and assessed the efficacy of DC-CIK cell-based immunotherapy combined with chemotherapy compared to treatment with chemotherapy alone. T cell subtypes, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated in each group. In total, 134 patients were included in the DC-CIK group and 121 patients were included in the control group. No significant differences were observed in the percentages of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), and NK cells after DC-CIK cell-based immunotherapy compared to before chemotherapy in the DC-CIK group. The median PFS and OS in the DC-CIK treatment group were 8.8 months (95 % CI 8.4-9.1) and 14.7 months (95 % CI 13.9-15.5), respectively, which were significantly improved compared to the PFS and OS in the control group. The frequencies of grade III and IV leukopenia (8.2 vs. 19.0 %, P = 0.011), grade III and IV anemia (3.0 vs. 9.1 %, P = 0.039), and grade III and IV thrombocytopenia (3.7 vs. 10.7 %, P = 0.029) were significantly lower in the DC-CIK group compared to the control group. DC-CIK cell-based immunotherapy could induce an immune response against colorectal cancer and prolong PFS and OS. DC-CIK cell-based immunotherapy combined with chemotherapy had a significant benefit in terms of survival in patients with colorectal cancer compared to chemotherapy alone.

Dual Functional Capability of Dendritic Cells – Cytokine-Induced Killer Cells in Improving Side Effects of Colorectal Cancer Therapy

“…Interactions between molecules on the surface of mature DCs and CIK cells cause an increased activation of each of these populations; however, the exact mechanism of action is still not fully understood. The stage of DCs maturation determines DC–CIK interaction and its function (Lin et al, 2016). Mature DCs provide necessary signals for proliferation of CIK cells by increasing their cytotoxic and cytolytic capabilities; immature DCs are unable to trigger this reaction and are consequently killed by CIK cells (Qu et al, 2014).…”

“…According to Zhu et al (2014; Lin et al, 2016), among 100 patients with CRC, more than 60% developed positive cell-mediated cytotoxicity response to the treatment with DC-CIK, assessed in DTH skin test. Adverse events occurred in less than 30% of recruited patients and included fever, insomnia, sore joints and skin rush (Niu et al, 2014; Zhang et al, 2016).…”

“…Dendritic cell-cytokine-induced killer cell-based immunotherapy combined with chemotherapy prolongs PFS in patients with CRC, and increases OS rate to almost 4 months, when compared to chemotherapy alone (Lin et al, 2016). Similar outcomes were reported in the study by Niu et al (2014) in which 44 out of 70 patients with CRC developed positive immune response after DC-CIK-based immunotherapy, which prolonged their MST.…”

“…The immunotherapy with DC-CIK reduces the severity of adverse effects, namely grade III and IV leukopenia, thrombocytopenia and anemia, which commonly occurs as a consequence of conventional cancer therapy, improves overall quality of life and prolongs the survival of CRC patients (Lin et al, 2016). …”

Microfluidic models for adoptive cell-mediated cancer immunotherapies

“…ACT relies on the isolation, genetic manipulation and reinfusion into patients of CD8 + T cells expressing antigen receptors for tumours to mediate an effector function. However, the use of other lymphocytes as natural killer (NK) cells [1], dendritic cells, cytokine-induced killer (DC-CIK) [s1]cells [2] and CD4 + helper T cells [3] could all be valid alternatives for cancer immunotherapy. We first review the present state of ACT for the personalised treatment of human cancers with its principal challenges to provide a context for potential microfluidics-based strategies for improvement at early stages of therapy design.…”