@article{bcf0c659b8a04282a11626fdb2aa3aa8,
title = "Targeting tumors with IL-21 reshapes the tumor microenvironment by proliferating PD-1intTim-3-CD8+ T cells",
abstract = "The lack of sufficient functional tumor-infiltrating lymphocytes in the tumor microenvironment (TME) is one of the primary indications for the poor prognosis of patients with cancer. In this study, we developed an Erbitux-based IL-21 tumor-targeting fusion protein (Erb-IL21) to prolong the half-life and improve the antitumor efficacy of IL-21. Compared with Erb-IL2, ErbIL21 demonstrated much lower toxicity in vivo. Mechanistically, Erb-IL21 selectively expanded functional cytotoxic T lymphocytes but not dysfunctional CD8+ T cells in the TME. We observed that the IL-21-mediated antitumor effect largely depended on the existing intratumoral CD8+ T cells, instead of newly migrated CD8+ T cells. Furthermore, Erb-IL21 overcame checkpoint blockade resistance in mice with advanced tumors. Our study reveals that Erb-IL21 can target IL-21 to tumors and maximize the antitumor potential of checkpoint blockade by expending a subset of tumor antigen-specific CD8+ T cells to achieve effective tumor control.",
author = "Sisi Deng and Zhichen Sun and Jian Qiao and Yong Liang and Longchao Liu and Chunbo Dong and Aijun Shen and Yang Wang and Hong Tang and Fu, {Yang Xin} and Hua Peng",
note = "Funding Information: We thank Casey Moore for reviewing the manuscript. We thank Haidong Tang, Meng Xu, Zhida Liu, Xue-zhi Cao, Yang Pu, Changzheng Lu, Zhenhua Ren, and Chuanhui Han for technical assistance. We thank Ximei Zhang, Yanfei Han, Shuaishuai Cao, Hairong Xu, Kaiting Yang, and Jingya Guo for technical assistance in the Institute of Biophysics. This work was supported by funding from the Chinese Academy of Sciences (KFJ-STS-ZDTP-062, 153831KYSB20160038, and XDA12020212 to HP). Funding Information: We thank Casey Moore for reviewing the manuscript. We thank Haidong Tang, Meng Xu, Zhida Liu, Xuezhi Cao, Yang Pu, Changzheng Lu, Zhenhua Ren, and Chuanhui Han for technical assistance. We thank Ximei Zhang, Yanfei Han, Shuaishuai Cao, Hairong Xu, Kaiting Yang, and Jingya Guo for technical assistance in the Institute of Biophysics. This work was supported by funding from the Chinese Academy of Sciences (KFJ-STS-ZDTP-062, 153831KYSB20160038, and XDA12020212 to HP). Publisher Copyright: Copyright: {\textcopyright} 2020, American Society for Clinical Investigation.",
year = "2020",
month = apr,
doi = "10.1172/JCI.INSIGHT.132000",
language = "English (US)",
volume = "5",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "7",
}