Tang Jun, Ramis-Cabrer Daniel, Wang Xuejie, Barreiro Esther
Pulmonology Department-Muscle Wasting & Cachexia in Chronic Respiratory Diseases & Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Biomedical Research Park (PRBB), C/Dr. Aiguader, 88, E-08003 Barcelona, Spain.
Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Biomedical Research Park (PRBB), C/Dr. Aiguader, 88, E-08003 Barcelona, Spain.
Cancers (Basel). 2019 Sep 4;11(9):1301. doi: 10.3390/cancers11091301.
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. 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, = 9/group) and non-treated control animals. 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. 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.
肺癌（LC）是全球主要的死亡原因之一。靶向多种免疫机制的免疫调节剂已被证明可通过诱导免疫微环境来减轻实验模型中的肿瘤负担。我们假设其他生物学机制可能也有助于在用免疫调节剂治疗的荷肺癌小鼠中减轻肿瘤负担。对注射LP07腺癌细胞并用单克隆抗体（CD-137、CTLA-4、PD-1和CD-19，每组 = 9只）治疗的BALB/c小鼠皮下肿瘤以及未治疗的对照动物的肿瘤重量、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和沉默调节蛋白-1）标志物进行了分析（免疫印迹法）。与未治疗的癌症小鼠相比，在单克隆抗体治疗动物的肿瘤中，肿瘤面积、重量和Ki-67显著降低，而T细胞计数、氧化应激、细胞凋亡、自噬、活化的p65和沉默调节蛋白-1标志物增加。免疫调节剂通过降低肿瘤增殖以及增加氧化应激、细胞凋亡、自噬和信号传导标志物来减轻肿瘤负担（减小肿瘤大小和重量），这可能干扰了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轻肿瘤负担的具体贡献。
