Profiling the dynamic expression of checkpoint molecules on cytokineinduced killer cells from non-small-cell lung cancer patients
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- 英文论文题名：Profiling the dynamic expression of checkpoint molecules on cytokineinduced killer cells from non-small-cell lung cancer patients
- 论文作者：Wang Jian ; Zhang Lin ; Yang Lili ; Wei Feng ; Sun Qian ; Ren Xiubao
- 英文论文作者：Wang Jian ; Zhang Lin ; Yang Lili ; Wei Feng ; Sun Qian ; Ren Xiubao ; Key Laboratory of Cancer Immunology and Biotherapy ; Tianjin Medical University Cancer Institute and Hospital
- 年：2016
- 作者机构：Key Laboratory of Cancer Immunology and Biotherapy,Tianjin Medical University Cancer Institute and Hospital;
- 英文论文关键词：checkpoint ; cytokine-induced killer cell(CIK) ; non-small-cell lung cancer(NSCLC) ; immunotherapy
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R734.2
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：2
- 文件大小：1334k
- 原文格式：D
- 会议级别：全国
摘要
Objective: In the last three years, clinical trials with blocking antibodies targeting checkpoint CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. However, checkpoint molecules on cytokine-induced killer(CIK) cell, a non-specific adoptive immunotherapy, remain unknown. In present study, we aimed to explore the dynamic expression pattern of eight major checkpoint molecules(CTLA-4, PD-1, PD-L1, TIM- 3, CEACAM-1, LAG-3, TIGIT and BTLA)on CIK cells from NSCLC patients, which might shed light on the development of NSCLC patient immunotherapy.Methods: Peripheral blood mononuclear cells from sixteen NSCLC patients enrolled were extracted. Informed consent was obtained from all subjects before entry into research. The lymphocytes were then isolated and cultured in AIM-V medium containing IL-1α, IL-2 and IFN-γ at 37°C with 5% CO2 humid atmosphere. The expression profile of checkpoint receptors was analyzed every three days throughout the culture by using the flow cytometry.Results: Except BTLA, the other molecules were sharply elevated at day 3 from culture. Thereafter, PD-1 and TIGIT expressions decreased gradually towards the initial level. Moreover, CTLA-4 faded away during the later stage of culture. LAG-3 expression decreased but was still significantly higher than day 0 level. Of note, PD-L1 remained high expression during CIK culture, indicating that PD-L1 might act as an inhibitory molecule on CIK cells. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation.Conclusion: These observations suggested that CIK cells might be partly exhausted before clinical transfusion, characterized by high expressions of PD-L1, LAG-3, TIM-3, and CEACAM-1. Our results imply that implementing combined treatment on CIK cells before transfusion by use of antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients.
Objective: In the last three years, clinical trials with blocking antibodies targeting checkpoint CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. However, checkpoint molecules on cytokine-induced killer(CIK) cell, a non-specific adoptive immunotherapy, remain unknown. In present study, we aimed to explore the dynamic expression pattern of eight major checkpoint molecules(CTLA-4, PD-1, PD-L1, TIM- 3, CEACAM-1, LAG-3, TIGIT and BTLA)on CIK cells from NSCLC patients, which might shed light on the development of NSCLC patient immunotherapy.Methods: Peripheral blood mononuclear cells from sixteen NSCLC patients enrolled were extracted. Informed consent was obtained from all subjects before entry into research. The lymphocytes were then isolated and cultured in AIM-V medium containing IL-1α, IL-2 and IFN-γ at 37°C with 5% CO_2 humid atmosphere. The expression profile of checkpoint receptors was analyzed every three days throughout the culture by using the flow cytometry.Results: Except BTLA, the other molecules were sharply elevated at day 3 from culture. Thereafter, PD-1 and TIGIT expressions decreased gradually towards the initial level. Moreover, CTLA-4 faded away during the later stage of culture. LAG-3 expression decreased but was still significantly higher than day 0 level. Of note, PD-L1 remained high expression during CIK culture, indicating that PD-L1 might act as an inhibitory molecule on CIK cells. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation.Conclusion: These observations suggested that CIK cells might be partly exhausted before clinical transfusion, characterized by high expressions of PD-L1, LAG-3, TIM-3, and CEACAM-1. Our results imply that implementing combined treatment on CIK cells before transfusion by use of antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients.
Objective: In the last three years, clinical trials with blocking antibodies targeting checkpoint CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. However, checkpoint molecules on cytokine-induced killer(CIK) cell, a non-specific adoptive immunotherapy, remain unknown. In present study, we aimed to explore the dynamic expression pattern of eight major checkpoint molecules(CTLA-4, PD-1, PD-L1, TIM- 3, CEACAM-1, LAG-3, TIGIT and BTLA)on CIK cells from NSCLC patients, which might shed light on the development of NSCLC patient immunotherapy.Methods: Peripheral blood mononuclear cells from sixteen NSCLC patients enrolled were extracted. Informed consent was obtained from all subjects before entry into research. The lymphocytes were then isolated and cultured in AIM-V medium containing IL-1α, IL-2 and IFN-γ at 37°C with 5% CO_2 humid atmosphere. The expression profile of checkpoint receptors was analyzed every three days throughout the culture by using the flow cytometry.Results: Except BTLA, the other molecules were sharply elevated at day 3 from culture. Thereafter, PD-1 and TIGIT expressions decreased gradually towards the initial level. Moreover, CTLA-4 faded away during the later stage of culture. LAG-3 expression decreased but was still significantly higher than day 0 level. Of note, PD-L1 remained high expression during CIK culture, indicating that PD-L1 might act as an inhibitory molecule on CIK cells. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation.Conclusion: These observations suggested that CIK cells might be partly exhausted before clinical transfusion, characterized by high expressions of PD-L1, LAG-3, TIM-3, and CEACAM-1. Our results imply that implementing combined treatment on CIK cells before transfusion by use of antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients.
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