Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor-Associated Macrophages for Cancer Immunotherapy.
Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor-Associated Macrophages for Cancer Immunotherapy.
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DOI：
10.1002/advs.202206001
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发表时间：
2023-02
期刊：
影响因子：
15.1
通讯作者：
Gu, Zhen
中科院分区：
文献类型：
--
作者：
Wen, Di;Liang, Tingxizi;Chen, Guojun;Li, Hongjun;Wang, Zejun;Wang, Jinqiang;Fu, Ruxing;Han, Xiao;Ci, Tianyuan;Zhang, Yuqi;Abdou, Peter;Li, Ruoxin;Bu, Linlin;Dotti, Gianpietro;Gu, Zhen
肿瘤相关脂肪细胞(TAA)招募单核细胞，并促进其分化为肿瘤相关巨噬细胞(TAM)，支持肿瘤的发展。在这里，TAA被设计成促进TAM的极化到肿瘤抑制的M1表型。Telratolimod是一种Toll样受体7/8激动剂，被装载到脂肪细胞的脂滴中，在肿瘤细胞触发脂解时在肿瘤部位释放。在黑色素瘤模型中，局部给药的脂肪细胞增加了原发和远处肿瘤中肿瘤抑制的M1巨噬细胞，并抑制了肿瘤的生长。此外，载药脂肪细胞改善了肿瘤微环境中CD8+T细胞介导的免疫反应，并有利于肿瘤引流淋巴结中的树突状细胞成熟。脂肪细胞被设计成招募巨噬细胞，并进一步输送脂质结合的Toll样受体7/8激动剂，使肿瘤相关的巨噬细胞极化到M1表型，用于癌症免疫治疗。通过利用肿瘤细胞触发的脂解作用，实现了肿瘤响应性药物的释放，全身抗肿瘤免疫反应抑制了原发和远处肿瘤的生长。
Tumor‐associated adipocytes (TAAs) recruit monocytes and promote their differentiation into tumor‐associated macrophages (TAMs) that support tumor development. Here, TAAs are engineered to promote the polarization of TAMs to the tumor suppressive M1 phenotype. Telratolimod, a toll‐like receptor 7/8 agonist, is loaded into the lipid droplets of adipocytes to be released at the tumor site upon tumor cell‐triggered lipolysis. Locally administered drug‐loaded adipocytes increased tumor suppressive M1 macrophages in both primary and distant tumors and suppressed tumor growth in a melanoma model. Furthermore, drug‐loaded adipocytes improved CD8+ T cell‐mediated immune responses within the tumor microenvironment and favored dendritic cell maturation in the tumor draining lymph nodes. The adipocytes are engineered to recruit macrophages and further deliver the lipid conjugated toll‐like receptor 7/8 agonist, which polarized the tumor‐associated macrophages to the M1 phenotype for cancer immunotherapy. By leveraging the tumor cell‐triggered lipolysis, a tumor‐responsive drug release is achieved and the systemic antitumor immune response suppressed both primary and distant tumor growth.
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DOI：
10.1158/1078-0432.ccr-16-3122
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brown JM;Recht L;Strober S
通讯作者：
Strober S
影响因子：
17.1
作者：
Kim, Sun-Young;Kim, Sohyun;Lim, Yong Taik
通讯作者：
Lim, Yong Taik
DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mantovani A;Marchesi F;Malesci A;Laghi L;Allavena P
通讯作者：
Allavena P
影响因子：
4.6
作者：
Hollmén M;Roudnicky F;Karaman S;Detmar M
通讯作者：
Detmar M
DOI：
10.1073/pnas.1314121111
发表时间：
2014-01-28
影响因子：
11.1
作者：
Desnues, Benoit;Macedo, Amanda Beatriz;Alexopoulou, Lena
通讯作者：
Alexopoulou, Lena