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  • Antitumor immunity targeting fibroblast activation protein-α in a mouse Lewis lung carcinoma model.

Antitumor immunity targeting fibroblast activation protein-α in a mouse Lewis lung carcinoma model.

Oncology letters (2020-06-23)
Junping Xie, Shiyang Yuan, Laishui Peng, Huanyu Li, Linxia Niu, Hui Xu, Xiaolin Guo, Mei Yang, Fengying Duan
摘要

The tumor stromal microenvironment is an integral part of the occurrence and development of tumor. Cancer-associated fibroblasts (CAFs) are a key component of most tumor stromal microenvironments. The present study aimed to investigate the use of CAFs-targeted immunotherapy to fibroblast activation protein-α (FAP-α) expressed in CAFs. Recombinant adenoviral vectors containing the mouse FAP-α cDNA (rAd-FAP-α) were constructed. C57BL/6 mice were immunized with rAd-FAP-α infected dendritic cells (DCs) against FAP-α, which is overexpress in CAFs. The results demonstrated that mice vaccinated with rAd-FAP-α DCs gave rise to potent FAP-α-specific cytotoxic T lymphocytes capable of lysing Lewis lung cancer (LLC) CAFs. Furthermore, mice vaccinated with rAd-FAP-α-transduced DCs induced an effective therapeutic or protective antitumor immunity to LLC in a subcutaneous model, and prolonged overall survival time compared with mice vaccinated with the control recombinant adenovirus-transduced DCs (rAd-c DCs) or DCs alone. The results of the present study suggested that FAP-α, which is preferentially expressed in CAFs, may be considered as a potential target for killing or destroying CAFs within the tumor stromal microenvironment, and may be exploited to develop immunogenic tumor vaccines.

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Sigma-Aldrich
OptiPrep密度梯度培养基, used for cell and subcellular organelle isolation