Profiling the dynamic expression of checkpoint molecules on cytokine-induced killer cells from non-small-cell lung cancer patients.
Immune checkpoints associate with dysfunctional T cells, which have a reduced ability to clear pathogens or cancer cells. T-cell checkpoint blockade may improve patient survival. However, checkpoint molecules on cytokine-induced killer (CIK) cell, a non-specific adoptive immunotherapy, remain unknown. In present study, we detected the dynamic expression 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. The majority of these molecules, except BTLA, were sharply elevated during the early stage of CIK cell culture. Thereafter, PD-1 and TIGIT expressions decreased gradually towards the initial level (day 0). Moreover, CTLA-4 faded away during the later stage of CIK culture. LAG-3 expression decreased but was still significantly higher than the initial level. Of note, PD-L1 remained stably upregulated during CIK culture compared with PD-1, indicating that PD-L1 might act as an inhibitory molecule on CIK cells instead of PD-1. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation. BTLA displayed a distinct pattern, and its expression gradually decreased throughout the CIK culture. These observations suggested that CIK cells might be partly exhausted before clinical transfusion, characterized by the high expression of PD-L1, LAG-3, TIM- 3, and CEACAM-1 and the low expression of TIGIT, BTLA, PD-1, and CTLA-4 compared with initial culture. Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients.
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Lin
L
Zhang
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Jian
J
Wang
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Feng
F
Wei
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Kaiyuan
K
Wang
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Qian
Q
Sun
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Fan
F
Yang
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Hao
H
Jin
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Yu
Y
Zheng
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Hua
H
Zhao
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Limei
L
Wang
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Wenwen
W
Yu
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Xiying
X
Zhang
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Yang
Y
An
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Lili
L
Yang
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Xinwei
X
Zhang
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.|National Clinical Research Center of Cancer, Tianjin, China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Xiubao
X
Ren
D000072283:A549 Cells; D000328:Adult; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy / Q000379:methods; D055612:Cytokine-Induced Killer Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000378:metabolism*
D000074322:Antineoplastic Agents, Immunological; D011971:Receptors, Immunologic
checkpoint molecule; cytokine-induced killer cell (CIK); immunotherapy; non-small-cell lung cancer (NSCLC)