MAP7D2 reduces CD8(+) cytotoxic T lymphocyte infiltration through MYH9-HMGB1 axis in colorectal cancer.
MAP7D2 reduces CD8(+) cytotoxic T lymphocyte infiltration through MYH9-HMGB1 axis in colorectal cancer.
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MAP7D2 通过 MYH9-HMGB1 轴减少结直肠癌中 CD8 细胞毒性 T 淋巴细胞浸润
DOI：
10.1016/j.ymthe.2022.09.001
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发表时间：
2023-01-04
影响因子：
12.4
通讯作者：
Wu, Xianrui
中科院分区：
文献类型：
--
作者：
Wu, Qian;Yue, Xiao;Liu, Huashan;Zhu, Yaxi;Ke, Haoxian;Yang, Xin;Yin, Shi;Li, Zhihao;Zhang, Yunfeng;Hu, Tuo;Lan, Ping;Wu, Xianrui
免疫检查点抑制剂（ICIS）代表了癌症免疫疗法的新范例，但在很大程度上可以受到CD8+细胞毒性T淋巴细胞（CTL）的有限限制，而在此处，下一个蛋白酶（MSS Serecratient），近距离（MSS）在下一型蛋白（not and Inder）（We ynot and Indy）。治疗性操作以提高ICI的效率CRC治疗在人CRC组织中，MAP7D2的表达显着增加，MAP7D2与抗肿瘤T淋巴细胞的存在不利iClate，map7d2相互作用使用MYH9并保护其免受泛素介导的降解，随后降低了HMGB1的分泌，这抑制了MSS CRC中CD8+ CTL的浸润，这些发现突出了MAP7D2在确定CD8+ CTLS和MAP的浸润中的重要性。
这项研究将MAP7D2确定为通过与MyH9相互作用并抑制HMGB1分泌来抑制CD8+ T细胞的重要驱动力。
Immune checkpoint inhibitors (ICIs) represent a new paradigm in cancer immunotherapy, but can be largely restricted by the limited presence of CD8+ cytotoxic T lymphocytes (CTLs) in colorectal cancer (CRC) patients with microsatellite stable (MSS) tumors. Here, through next-generation sequencing, we identify microtubule-associated protein 7 domain 2 (MAP7D2) as an exploitable therapeutic maneuver to improve the efficacy of ICIs for MSS CRC therapy. In human CRC tissues, MAP7D2 expression is significantly increased in MSS CRC, and MAP7D2 adversely correlates with the presence of antitumor T lymphocytes. In vitro and in vivo experiments demonstrate that MAP7D2 knockdown significantly increases the infiltration of CD8+ CTLs, thereby inhibiting tumor progression and improving the efficacy of ICIs in MSS CRC murine models. Mechanistically, MAP7D2 interacts with MYH9 and protects it from ubiquitin-mediated degradation, subsequently decreasing the secretion of HMGB1, which suppresses the infiltration of CD8+ CTLs in MSS CRC. These findings highlight the importance of MAP7D2 in determining the infiltration of CD8+ CTLs and indicate that targeting MAP7D2 in MSS CRC may present a novel antitumor immunotherapy. This study identified MAP7D2 as a vital driver in suppressing CD8+ T cells infiltration by interacting with MYH9 and inhibiting HMGB1 secretion. The MAP7D2-MYH9-HMGB1 axis may serve as the exploitable therapeutic target in the ICIs-based combinational therapy for CRC patients.
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影响因子：
29.4
作者：
Hu T;Shukla SK;Vernucci E;He C;Wang D;King RJ;Jha K;Siddhanta K;Mullen NJ;Attri KS;Murthy D;Chaika NV;Thakur R;Mulder SE;Pacheco CG;Fu X;High RR;Yu F;Lazenby A;Steegborn C;Lan P;Mehla K;Rotili D;Chaudhary S;Valente S;Tafani M;Mai A;Auwerx J;Verdin E;Tuveson D;Singh PK
通讯作者：
Singh PK
突变的 KRAS 触发结直肠癌中肿瘤相关巨噬细胞的功能重编程
影响因子：
39.3
作者：
Liu H;Liang Z;Zhou C;Zeng Z;Wang F;Hu T;He X;Wu X;Wu X;Lan P
通讯作者：
Lan P
神经元膜交通的极性需要在微管相关的SEPTIN进入树突期间对运动蛋白运动货物进行排序。
影响因子：
11.8
作者：
Karasmanis EP;Phan CT;Angelis D;Kesisova IA;Hoogenraad CC;McKenney RJ;Spiliotis ET
通讯作者：
Spiliotis ET
影响因子：
10.9
作者：
Fortis SP;Sofopoulos M;Sotiriadou NN;Haritos C;Vaxevanis CK;Anastasopoulou EA;Janssen N;Arnogiannaki N;Ardavanis A;Pawelec G;Perez SA;Baxevanis CN
通讯作者：
Baxevanis CN
影响因子：
10.9
作者：
Gao, Qun;Wang, Shumin;Zhang, Yi
通讯作者：
Zhang, Yi