Knockout of high-mobility group box 1 in B16F10 melanoma cells induced host immunity-mediated suppression of in vivo tumor growth.
Knockout of high-mobility group box 1 in B16F10 melanoma cells induced host immunity-mediated suppression of in vivo tumor growth.
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DOI：
10.1007/s12032-022-01659-2
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发表时间：
2022-02-12
期刊：
影响因子：
--
通讯作者：
Yamada A
中科院分区：
文献类型：
--
作者：
Yokomizo K;Waki K;Ozawa M;Yamamoto K;Ogasawara S;Yano H;Yamada A
高迁移率族蛋白1（HMGB 1）是一种损伤相关的分子模式（DAMP）分子，从受损或死亡的细胞中释放，诱导炎症和随后的先天免疫。然而，HMGB 1在抗肿瘤免疫中的作用尚不清楚，因为肿瘤微环境中的炎症也有助于肿瘤的促进和进展。在本研究中，我们使用CRISPR/Cas9系统通过基因组编辑从B16 F10和CT 26小鼠肿瘤中建立了HMGB 1敲除克隆，并研究了HMGB 1在抗肿瘤免疫中的作用。我们发现（1）在肿瘤细胞中敲除HMGB 1在体内抑制肿瘤生长，但在体外不抑制肿瘤生长;（2）体内肿瘤生长的抑制是由CD 8 T细胞介导的;（3）在HMGB 1敲除的肿瘤中，CD 8 T细胞、巨噬细胞和树突状细胞向肿瘤组织中的浸润加速。这些结果表明，敲除肿瘤细胞中的HMGB 1将肿瘤从称为“冷”的免疫细胞浸润不良转化为“免疫炎症”或“热”，并抑制细胞毒性T淋巴细胞介导的体内肿瘤生长。免疫细胞向肿瘤微环境的浸润是被称为癌症免疫循环的系列中的重要步骤。因此，对肿瘤来源的HMGB 1的操纵可能适用于改善癌症免疫疗法的临床结果，包括免疫检查点阻断和癌症疫苗疗法。在线版本包含补充材料，可通过10.1007/s12032-022-01659-2获得。
High-mobility group box 1 (HMGB1) has been reported as a damage-associated molecular pattern (DAMP) molecule that is released from damaged or dead cells and induces inflammation and subsequent innate immunity. However, the role of HMGB1 in the anti-tumor immunity is unclear since inflammation in the tumor microenvironment also contributes to tumor promotion and progression. In the present study, we established HMGB1-knockout clones from B16F10 and CT26 murine tumors by genome editing using the CRISPR/Cas9 system and investigated the role of HMGB1 in anti-tumor immunity. We found that (1) knockout of HMGB1 in the tumor cells suppressed in vivo, but not in vitro, tumor growth, (2) the suppression of the in vivo tumor growth was mediated by CD8 T cells, and (3) infiltration of CD8 T cells, macrophages and dendritic cells into the tumor tissues was accelerated in HMGB1-knockout tumors. These results demonstrated that knockout of HMGB1 in tumor cells converted tumors from poor infiltration of immune cells called “cold” to “immune-inflamed” or “hot” and inhibited in vivo tumor growth mediated by cytotoxic T lymphocytes. Infiltration of immune cells to the tumor microenvironment is an important step in the series known as the cancer immunity cycle. Thus, manipulation of tumor-derived HMGB1 might be applicable to improve the clinical outcomes of cancer immunotherapies, including immune checkpoint blockades and cancer vaccine therapies. The online version contains supplementary material available at 10.1007/s12032-022-01659-2.
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影响因子：
9
作者：
Fucikova J;Kepp O;Kasikova L;Petroni G;Yamazaki T;Liu P;Zhao L;Spisek R;Kroemer G;Galluzzi L
通讯作者：
Galluzzi L
影响因子：
10.6
作者：
Kang, Rui;Chen, Ruochan;Zhang, Qiuhong;Hou, Wen;Wu, Sha;Cao, Lizhi;Huang, Jin;Yu, Yan;Fan, Xue-gong;Yan, Zhengwen;Sun, Xiaofang;Wang, Haichao;Wang, Qingde;Tsung, Allan;Billiar, Timothy R.;Zeh, Herbert J., III;Lotze, Michael T.;Tang, Daolin
通讯作者：
Tang, Daolin
影响因子：
30.5
作者：
Chiba, Shigeki;Baghdadi, Muhammad;Akiba, Hisaya;Yoshiyama, Hironori;Kinoshita, Ichiro;Dosaka-Akita, Hirotoshi;Fujioka, Yoichiro;Ohba, Yusuke;Gorman, Jacob V.;Colgan, John D.;Hirashima, Mitsuomi;Uede, Toshimitsu;Takaoka, Akinori;Yagita, Hideo;Jinushi, Masahisa
通讯作者：
Jinushi, Masahisa
影响因子：
45.3
作者：
Massard, Christophe;Gordon, Michael S.;Segal, Neil H.
通讯作者：
Segal, Neil H.
DOI：
10.1158/1078-0432.ccr-13-0495
发表时间：
2013-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kang R;Zhang Q;Zeh HJ 3rd;Lotze MT;Tang D
通讯作者：
Tang D