Low-Dose Gemcitabine Treatment Enhances Immunogenicity and Natural Killer Cell-Driven Tumor Immunity in Lung Cancer
Low-Dose Gemcitabine Treatment Enhances Immunogenicity and Natural Killer Cell-Driven Tumor Immunity in Lung Cancer
复制标题
低剂量吉西他滨治疗增强肺癌的免疫原性和自然杀伤细胞驱动的肿瘤免疫
DOI：
10.3389/fimmu.2020.00331
复制
发表时间：
2020-02-25
影响因子：
7.3
通讯作者：
Xu, Lijun
中科院分区：
文献类型：
--
作者：
Zhang, Xin;Wang, Dong;Xu, Lijun
吉西他滨已被用作肺癌的一线化疗药物，但许多患者会出现癌症复发。激活体内抗肿瘤免疫已成为预防肿瘤复发的重要途径。抗肿瘤免疫反应往往依赖于肿瘤的免疫原性。在我们的研究中，我们观察到低剂量吉西他滨治疗通过增加钙调蛋白、高迁移率组1的暴露和上调NKG2D配体的表达来增强肺癌的免疫原性。进一步的研究表明，低剂量吉西他滨治疗增加了小鼠干扰素-γ的表达和nk细胞的活化。低剂量吉西他滨治疗足以抑制肿瘤生长，体内副作用少。这些数据表明，低剂量吉西他滨诱导的免疫化疗激活了免疫功能正常患者的抗肿瘤免疫。
Gemcitabine has been used as first-line chemotherapy against lung cancer, but many patients experience cancer recurrence. Activation of anti-tumor immunity in vivo has become an important way to prevent recurrence. Anti-tumor immune responses are often dependent upon the immunogenicity of tumors. In our study, we observed that low-dose gemcitabine treatment enhanced the immunogenicity of lung cancer by increasing the exposure of calreticulin, high mobility group box 1, and upregulating expression of NKG2D ligands. Further studies demonstrated that low-dose gemcitabine treatment increased interferon-γ expression and NK-cell activation in mice. Low-dose gemcitabine treatment was sufficient for inhibiting tumor growth with few side effects in vivo. These data suggest that low-dose gemcitabine-induced immunochemotherapy activated antitumor immunity in immunocompetent patients.