Xiaofeng Huang1, Jing Zhang1, Xiaolong Li1, Hongxing Huang2, Ying Liu3, Mei Yu1, Yan Zhang4, Hua Wang5. 1. Department of Oral and Maxillofacial Surgery, Clinical Laboratory, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, PR China. 2. Laboratory of Cancer and Stem Cell Biology, Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China. 3. Laboratory of Cancer and Stem Cell Biology, Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China; Guangzhou Yidai Pharmaceutical Co., Ltd, Guangzhou 510055, PR China. 4. Laboratory of Cancer and Stem Cell Biology, Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China. Electronic address: zhang39@mail.sysu.edu.cn. 5. Department of Oral and Maxillofacial Surgery, Clinical Laboratory, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, PR China; Guangzhou Yidai Pharmaceutical Co., Ltd, Guangzhou 510055, PR China. Electronic address: wanghua9@mail.sysu.edu.cn.
Abstract
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-γ, TNF-α, 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.
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-γ, TNF-α, 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.