CD40 monoclonal antibody and OK432 synergistically promote the activation of dendritic cells in immunotherapy.
CD40 monoclonal antibody and OK432 synergistically promote the activation of dendritic cells in immunotherapy.
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CD40单抗和OK432协同促进树突状细胞在免疫治疗中的激活。
DOI：
10.1186/s12935-022-02630-x
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发表时间：
2022-06-17
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
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作者：
结直肠癌（CRC）肺转移通常表明预后不良，而患者可能受益于过继细胞治疗。肿瘤特异性细胞毒性T淋巴细胞（CTL）已被报道为CRC的有希望的治疗。然而，CTL的抗肿瘤作用仍然有限，部分原因是通过抗原呈递树突状细胞（DC）的活化产生的效应细胞不足。本研究表明，CD 40 mAb和Picibanil（OK-432）的组合可以显著增强DC在体外和体内对CTL的激活。采用流式细胞术、结肠癌小鼠模型、病理染色等方法研究其特异性功能。这种方法促进了DC的成熟，增加了刺激性细胞因子的产生，并抑制了抑制性细胞因子的分泌。此外，它通过刺激CTL增殖而抑制TcB的数量，同时伴随着相应细胞因子的正向调节，从而促进CTL的杀伤效率。此外，该组合单元可以阻止结肠癌小鼠模型中转移性肺上肿瘤细胞的扩增。总的来说，CD 40-mAb和OK-432的组合促进了DC的成熟并增强了T细胞的细胞毒性，这是有希望的针对CRC的治疗方法。在线版本包含补充材料，可通过10.1186/s12935-022-02630-x获得。
Colorectal cancer (CRC) with pulmonary metastasis usually indicates a poor prognosis, whereas patients may benefit from adoptive cell therapy. Tumor-specific cytotoxic T lymphocytes (CTLs) have been reported as a promising treatment for CRC. However, the antitumor effect of CTLs remains limited partially due to insufficient production of effector cells via the activation by antigen-presenting dendritic cells (DCs). This study showed that a combination of CD40 mAb and Picibanil (OK-432) could significantly enhance the activation of CTLs by DCs, both in vitro and in vivo. Flow cytometry, colon cancer mouse model, and pathological staining were employed to demonstrate the specific functions. This approach promoted the maturation of DCs, augmented the production of stimulatory cytokines, and suppressed the secretion of inhibitory cytokines. Additionally, it facilitated the killing efficiency of CTLs via stimulating their proliferation while restraining the number of Tregs, concomitantly with the positive regulation of corresponding cytokines. Furthermore, the combined unit could hurdle the expansion of tumor cells on metastatic lungs in the colon cancer mouse model. Collectively, the combination of CD40-mAb and OK-432 facilitated the maturation of DCs and enhanced the cytotoxicity of T cells, promising therapeutic approach against CRC. The online version contains supplementary material available at 10.1186/s12935-022-02630-x.
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影响因子：
1.1
作者：
通讯作者：
--
影响因子：
11.5
作者：
Bol, Kalijn F.;Schreibelt, Gerty;Figdor, Carl G.
通讯作者：
Figdor, Carl G.
影响因子：
--
作者：
Inaba, Kayo;Swiggard, William J;Brinster, Carine
通讯作者：
Brinster, Carine
影响因子：
5.2
作者：
El Sissy C;Kirilovsky A;Zeitoun G;Marliot F;Haicheur N;Lagorce-Pagès C;Galon J;Pagès F
通讯作者：
Pagès F
影响因子：
5.2
作者：
Djureinovic D;Wang M;Kluger HM
通讯作者：
Kluger HM