Tetracyclines Enhance Anti-tumor T-Cell Responses Induced by a Bispecific T-Cell Engager
Tetracyclines Enhance Anti-tumor T-Cell Responses Induced by a Bispecific T-Cell Engager
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DOI：
10.1248/bpb.b21-00806
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发表时间：
2022-04-01
影响因子：
2
通讯作者：
Wada, Hisashi
中科院分区：
文献类型：
--
作者：
Noguchi, Yuki;Yamamoto, Yoko;Wada, Hisashi
癌症免疫疗法是癌症患者强有力的治疗选择。为了提高癌症免疫疗法的治疗效果，我们计划开发新的免疫刺激药物与癌症免疫疗法联合使用。在目前的研究中，我们主要关注四环素类药物，其对免疫治疗的影响存在争议。我们检测了四环素对健康供者外周血和非小细胞肺癌（NSCLC）患者肿瘤组织中人类T细胞的影响。通过使用双特异性T细胞参与技术评估外周T细胞对肿瘤细胞的细胞毒性，我们发现四环素（二甲胺四环素、四环素、多西环素、美环素、金四环素和去环素）通过颗粒酶B表达和CD4+和CD8+ T细胞增殖增强T细胞的细胞毒性。在对非小细胞肺癌患者外周血单核细胞（PBMCs）和肺肿瘤浸润细胞的分析中，我们发现去环环素不仅增强了外周血单核细胞（PBMCs）的t细胞毒性，而且增强了肺肿瘤组织的t细胞毒性。这些结果支持了四环素类药物在癌症免疫联合治疗中的进一步应用。
Cancer immunotherapies are powerful therapeutic options for cancer patients. To enhance the therapeutic effects of cancer immunotherapies, we plan to develop novel immunostimulatory drugs for use in combination with cancer immunotherapy. In the present study, we focused on tetracyclines, the effects of which are controversial for immunotherapy. We examined the effects of tetracyclines on human T cells in the peripheral blood of healthy donors and the tumor tissues of non-small cell lung cancer (NSCLC) patients. By using bispecific T-cell engager technology to assess the cytotoxicity of peripheral T cells against tumor cells, we showed that tetracyclines (minocycline, tetracycline, doxycycline, meclocycline, chlortetracycline, and demeclocycline) enhanced T-cell cytotoxicity through granzyme B expression and CD4+ and CD8+ T-cell proliferation. In analyses of the peripheral blood mononuclear cells (PBMCs) and lung tumor-infiltrated cells of NSCLC patients, we found that demeclocycline enhanced T-cell cytotoxicity not only in PBMCs, but also in lung tumor tissues. These results support the further application of tetracyclines to combination cancer immunotherapy.