Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events
Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events
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DOI：
10.3390/cancers11091301
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发表时间：
2019-09
期刊：
影响因子：
5.2
通讯作者：
Jun Tang;D. Ramis-Cabrer;Xuejie Wang;E. Barreiro
中科院分区：
文献类型：
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作者：
Jun Tang;D. Ramis-Cabrer;Xuejie Wang;E. Barreiro
背景：肺癌（LC）是全世界死亡的主要原因。事实证明，针对多种免疫机制的免疫调节剂可以通过诱导免疫微环境来减轻实验模型中的肿瘤负荷。我们假设其他生物学机制也可能有利于减少接受免疫调节剂治疗的肺癌小鼠的肿瘤负荷。方法：对注射单克隆抗体（CD-137、CTLA-4、PD-1 和 CD-19，N = 9/组）处理的 LP07 腺癌细胞的 BALB/c 小鼠和未处理对照的皮下肿瘤中的肿瘤重量、面积、T 细胞和肿瘤生长（免疫组织化学）、氧化应激、细胞凋亡、自噬和信号传导（NF-κB 和 Sirtuin-1）标记物进行分析（免疫印迹）动物。结果：与未治疗的癌症小鼠相比，在单克隆治疗的动物肿瘤中，肿瘤面积、重量和 ki-67 显着减少，而 T 细胞计数、氧化应激、细胞凋亡、自噬、激活的 p65 和 Sirtuin-1 标记物增加。结论：免疫调节剂通过减少肿瘤增殖和增加氧化应激、细胞凋亡、自噬和信号标记来减少肿瘤负荷（减小肿瘤大小和重量），这可能干扰肿瘤微环境的免疫特征。未来的研究应致力于阐明每种生物学机制对减少肿瘤负荷的具体贡献。
Background: Lung cancer (LC) is a major leading cause of death worldwide. Immunomodulators that target several immune mechanisms have proven to reduce tumor burden in experimental models through induction of the immune microenvironment. We hypothesized that other biological mechanisms may also favor tumor burden reduction in lung cancer-bearing mice treated with immunomodulators. Methods: Tumor weight, area, T cells and tumor growth (immunohistochemistry), oxidative stress, apoptosis, autophagy, and signaling (NF-κB and sirtuin-1) markers were analyzed (immunoblotting) in subcutaneous tumor of BALB/c mice injected with LP07 adenocarcinoma cells treated with monoclonal antibodies (CD-137, CTLA-4, PD-1, and CD-19, N = 9/group) and non-treated control animals. Results: Compared to non-treated cancer mice, in tumors of monoclonal-treated animals, tumor area and weight and ki-67 were significantly reduced, while T cell counts, oxidative stress, apoptosis, autophagy, activated p65, and sirtuin-1 markers were increased. Conclusions: Immunomodulators elicited a reduction in tumor burden (reduced tumor size and weight) through decreased tumor proliferation and increased oxidative stress, apoptosis, autophagy, and signaling markers, which may have interfered with the immune profile of the tumor microenvironment. Future research should be devoted to the elucidation of the specific contribution of each biological mechanism to the reduced tumor burden.