Low dose irradiation increases adoptive cytotoxic T lymphocyte migration in gastric cancer.
Low dose irradiation increases adoptive cytotoxic T lymphocyte migration in gastric cancer.
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DOI：
10.3892/etm.2017.5305
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发表时间：
2017-12
影响因子：
2.7
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Du J;Su S;Li H;Shao J;Meng F;Yang M;Qian H;Zou Z;Qian X;Liu B
过继细胞免疫疗法(ACI)已被证明是一种很有前途的癌症治疗方法;然而，过继免疫细胞向肿瘤的低效迁移是ACI的限速因素之一。本研究探讨2gy低剂量照射（LDI）是否能够增加过继淋巴细胞向胃癌细胞的迁移。2 Gy LDI处理导致胃癌细胞株产生显著的趋化因子（C-X-C基序）配体9 （CXCL9）和CXCL10。Transwell室迁移试验表明，LDI治疗后，细胞毒性T淋巴细胞向胃癌细胞的迁移增强。经2 Gy LDI治疗裸鼠胃癌后，静脉注射标记免疫细胞，在小鼠体内肿瘤部位观察到荧光信号集中，在LDI 8 h时荧光信号达到峰值。流式细胞术还观察到肿瘤部位的过继T细胞数量增加。此外，一项接受ACI联合2gy LDI治疗的转移性胃癌患者的病例研究进一步证明，2gy LDI能够将抗肿瘤效应T细胞募集到肿瘤部位。因此，利用2gy LDI将肿瘤转化为炎性外周组织的能力，可以克服抗肿瘤免疫反应效应期的障碍，提高免疫治疗的疗效。
Adoptive cellular immunotherapy (ACI) has been demonstrated to be a promising cancer therapeutic; however, the inefficient migration of adoptive immune cells to tumors is one of the rate-limiting factors of ACI. The present study investigated whether 2 Gy low dose irradiation (LDI) was able to increase the migration of adoptive lymphocytes to gastric cancer cells. Treatment with 2 Gy LDI resulted in marked chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 production from gastric cancer cell lines. A Transwell chamber migration assay demonstrated enhanced transmigration of cytotoxic T lymphocytes to gastric cancer cells following LDI treatment. After 2 Gy LDI application to established gastric carcinoma in nude mice, labeled immune cells were infused by intravenous injection and concentrated fluorescence signals were observed at the tumor sites within the mice, with a peak signal at 8-h LDI. Increased numbers of adoptive T cells at the tumor sites were also observed using flow cytometry. Furthermore, a case study of a patient with metastatic gastric cancer who had received ACI treatment combined with 2 Gy LDI provided further evidence that 2 Gy LDI is able to recruit antitumor effector T cells to tumor sites. Therefore, the ability of 2 Gy LDI to convert tumors into inflamed peripheral tissues may be exploited to overcome obstacles at the effector phase of the antitumor immune response and improve the therapeutic efficacy of immunotherapy.
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影响因子：
3.4
作者：
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