Rescue of iCIKs transfer from PD-1/PD-L1 immune inhibition in patients with resectable tongue squamous cell carcinoma (TSCC).

OBJECTIVES: The purpose of this study is to evaluate the therapeutic efficacy and the role of PD-1/PD-L1 pathway in tongue squamous cell carcinoma (TSCC) patients treated with radical operation combined with chemotherapy and improving cytokine induced killer cells (iCIKs) transfer. METHODS: Thirteen patients who received radical resection and chemotherapy were enrolled in this study. PD-1/PD-L1 expression was evaluated in TSCC patients. ICIKs were cultured from patient-derived peripheral blood mononuclear cells (PBMCs) in vitro. The immunological differences underlying iCIKs transfer were investigated through phenotype, cytokine secretion and PD-1/PD-L1 inhibition analysis. RESULTS: The serum PD-L1 levels were elevated in the TSCC patients. PD-L1 was detected on both human TSCC cells and tumour tissue sections. PD-1 expression was much higher on the PBMCs of TSCC patients than on in vitro cultured iCIKs. Interruption of PD-1/PD-L1 interaction enhanced the cytotoxicity of iCIKs in vitro. CD3 + CD8+ T cell proportion and cytokine IL-6 secretion decreased after chemotherapy. The infusion of iCIKs effectively reversed the immunosuppression through the upregulation of the CD3 + CD8+ T cell proportion and Th cell cytokine secretion (IFN-gamma, TNF-alpha, IL-4 and IL-6). Twelve responders are currently alive (95.7+ months), another patient 83 months. CONCLUSION: Our findings indicated that the PD-1/PD-L1 interaction contributes to the immunosuppression in TSCC patients. ICIKs transfer is an effective therapy to reverse the immunosuppression caused by surgical procedures and chemotherapy and improve immune system function.