Abstract
BackgroundSmall cell lung cancer (SCLC) relapses rapidly after the initial response to chemotherapy and shows drug-resistance. This study was to investigate the efficacy and safety of cellular immunotherapy (CIT) with autologous natural killer (NK), γδT, and cytokine-induced killer (CIK) cells as maintenance therapy for SCLC patients.MethodsA pilot prospective cohort study was conducted with SCLC patients who had responded to initial chemotherapy. Patients elected to receive either CIT as maintenance therapy (study group), or to be followed-up without further treatment (control group). Progression-free survival (PFS), overall survival (OS), and adverse effects were investigated.ResultsWe recruited 58 patients (29 in each group). The patient characteristics of the 2 groups were well balanced. PFS was not significantly different between the groups, but OS was significantly longer in the study group than the control (20 vs. 11.5 months, P = 0.005; hazard ratio [HR], 0.434, 95 % confidence interval [CI], 0.236–0.797, P = 0.007). Among patients with limited-stage disease, there was no difference in PFS between the groups, but OS was longer in the study group compared to the control (26.5 vs. 11.8 months, P = 0.033; HR, 0.405, 95 % CI, 0.169–0.972, P = 0.043). Among patients with extensive-stage disease, both PFS and OS were longer in the study group than the control (5 vs. 2.7 months, P = 0.037; HR, 0.403, 95 % CI, 0.162–1.003, P = 0.051, and 14.5 vs. 9 months, P = 0.038; HR, 0.403, 95 % CI, 0.165–0.987, P = 0.047, respectively). No significant adverse reactions occurred in patients undergoing CIT.ConclusionsCIT maintenance therapy in SCLC prolonged survival with only minimal side effects. Integrating CIT into current treatment may be a novel strategy for SCLC therapy, although further multi-center randomized studies are needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0514-0) contains supplementary material, which is available to authorized users.
Highlights
Small cell lung cancer (SCLC) relapses rapidly after the initial response to chemotherapy and shows drug-resistance
ΓδT cells can induce the natural killer (NK) cell-mediated killing of cancers that are usually resistant to NK cytolysis [22] and cross-present tumor antigens to CD8+ cytotoxic T lymphocyte (CTL) to mediate adaptive immune responses [23]. These findings suggest that the combined application of NK, γδT and cytokine-induced killer (CIK) cells may provide significantly synergistic anti-cancer effects via different mechanisms, and could provide effective cellular immunotherapy (CIT) for SCLC patients
Two extensive stage SCLC (ES-SCLC) patients in CIT group had one solitary pulmonary lesion highly suspected as lung cancer under the computed tomography (CT) scan
Summary
Small cell lung cancer (SCLC) relapses rapidly after the initial response to chemotherapy and shows drug-resistance. Despite a high initial response rate to first-line therapy, most patients die rapidly from recurrent, drug-. Some of them were failed, such as the dendritic cell-based p53 vaccine [10], but some of them obtained a certain effect, such as phased ipilimumab (an antibody against cytotoxic T-lymphocyte antigen-4 [CTLA-4]) with paclitaxel/carboplatin exhibited improved immune-related PFS (irPFS) [11]. It indicated that immunotherapy might have the potential to improve the prognosis of SCLC. Increasing attention has been paid to the possibility of immunotherapy for SCLC patients in recent years
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