Pan Jiang1, Yan Zhang2, Steve J Archibald3, Hua Wang4. 1. Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China. 2. Laboratory of Cancer and Stem Cell Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou 510055, China. 3. Positron Emission Tomography Research Centre, Department of Chemistry, University of Hull, Cottingham Road, Hull HU6 7RX, UK. 4. Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China; Guangzhou Yidai Pharmaceutical Co., Ltd, Guangzhou 510055, China. Electronic address: wanghua9@mail.sysu.edu.cn.
Abstract
OBJECTIVES: The aims of this study were to evaluate the therapeutic efficacy and to determine the immune factors for treatment success in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemotherapy followed by adoptive cell transfer (ACT). METHODS: A total of 43 HNSCC patients who received radical resection and chemotherapy were analysed in this study. Twenty-one of the patients were repeatedly treated with ACT after chemotherapy (ACT group), and the other twenty-two patients without ACT treatment were included as part of the control group. To investigate the immunological differences underlying these observations, we expanded and profiled improving cytokine-induced killer cells (iCIK) from peripheral blood mononuclear cells (PBMCs) with the timed addition of RetroNectin, OKT3 mAb, IFN γ and IL-2. RESULTS: The median of progression-free survival (PFS) and overall survival (OS) in the ACT group were significantly higher as compared to the control group (56 vs. 40; 58 vs. 45 months). In iCIK culture, there was a significant reduction in CD3+CD4+ T-cell proliferation and cytokines (IL-2, TNF) production from patients who received chemotherapy compared to patients without chemotherapy. Intra-arterial infusion of iCIK, in coordination with chemotherapy, considerably rescued iCIK culture from the suppression of systemic immunity induced by chemotherapy and induced tumour regression. CONCLUSIONS: Altogether, these findings suggest that ACT is an effective neo-adjuvant therapy for rescuing systemic immune suppression and improving survival time in patients with HNSCC.
OBJECTIVES: The aims of this study were to evaluate the therapeutic efficacy and to determine the immune factors for treatment success in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemotherapy followed by adoptive cell transfer (ACT). METHODS: A total of 43 HNSCCpatients who received radical resection and chemotherapy were analysed in this study. Twenty-one of the patients were repeatedly treated with ACT after chemotherapy (ACT group), and the other twenty-two patients without ACT treatment were included as part of the control group. To investigate the immunological differences underlying these observations, we expanded and profiled improving cytokine-induced killer cells (iCIK) from peripheral blood mononuclear cells (PBMCs) with the timed addition of RetroNectin, OKT3 mAb, IFN γ and IL-2. RESULTS: The median of progression-free survival (PFS) and overall survival (OS) in the ACT group were significantly higher as compared to the control group (56 vs. 40; 58 vs. 45 months). In iCIK culture, there was a significant reduction in CD3+CD4+ T-cell proliferation and cytokines (IL-2, TNF) production from patients who received chemotherapy compared to patients without chemotherapy. Intra-arterial infusion of iCIK, in coordination with chemotherapy, considerably rescued iCIK culture from the suppression of systemic immunity induced by chemotherapy and induced tumour regression. CONCLUSIONS: Altogether, these findings suggest that ACT is an effective neo-adjuvant therapy for rescuing systemic immune suppression and improving survival time in patients with HNSCC.