In vivo-edited CCR7+IL-7+ DCs reverse T cell exhaustion by promoting T memory stem cell differentiation
- 1Department of Clinical Pharmacy, The Second Qilu Hospital of Shandong University, Jinan 250033, P.R. China
Abstract
T cell exhaustion presents a challenge for antitumor immunotherapy. T memory stem cells (Tscms), whose ability to self-renew can continuously generate effector T cells, offering a way to reverse T cell exhaustion. Here, we propose a Tscm regulation strategy involving the construction of dendritic cell (DC)-targeting CCR7/IL-7 mRNA liposomes to edit CCR7+IL-7+ DCs in vivo, thus directly promoting Tscm differentiation within tumor-draining lymph nodes (TDLNs). The antigen-presenting CCR7+IL-7+ DCs migrate to the T-zone within TDLNs via CCR7-mediated signaling and secrete IL-7 to induce naive T cells to differentiate into Tscms. The antigens activate Tscms, promoting continuous Tscm self-renewal and effector T cell generation. The powerful antitumor effects have been observed in B16F10 and 4T1 tumor-bearing mice, and 80% of the mice exhibited suppressed distant tumor formation in the B16F10 prevention model. Overall, this research highlights the importance of Tscm abundance for antitumor immunotherapy and provides high clinical value for developing cancer vaccines.
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BibTeX
@article{fu2026vivoedited,
title = {{In vivo-edited CCR7+IL-7+ DCs reverse T cell exhaustion by promoting T memory stem cell differentiation}},
author = {Shunli Fu and Qingping Ma and Shuying Gao and Zhenxing Xia and Weiwei Mu and Shuang Liang and Shijun Yuan and Jinhu Liu and Yiming Xia and Xinrui Liu and Leiqiang Han and Yongjun Liu and Na Zhang},
journal = {Cell Reports Medicine},
year = {2026},
month = sep,
doi = {10.1016/j.xcrm.2026.103086},
url = {https://doi.org/10.1016/j.xcrm.2026.103086},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - In vivo-edited CCR7+IL-7+ DCs reverse T cell exhaustion by promoting T memory stem cell differentiation
AU - Shunli Fu
AU - Qingping Ma
AU - Shuying Gao
AU - Zhenxing Xia
AU - Weiwei Mu
AU - Shuang Liang
AU - Shijun Yuan
AU - Jinhu Liu
AU - Yiming Xia
AU - Xinrui Liu
AU - Leiqiang Han
AU - Yongjun Liu
AU - Na Zhang
PY - 2026
DA - 2026/09/30
JO - Cell Reports Medicine
DO - 10.1016/j.xcrm.2026.103086
UR - https://doi.org/10.1016/j.xcrm.2026.103086
AB - T cell exhaustion presents a challenge for antitumor immunotherapy. T memory stem cells (Tscms), whose ability to self-renew can continuously generate effector T cells, offering a way to reverse T cell exhaustion. Here, we propose a Tscm regulation strategy involving the construction of dendritic cell (DC)-targeting CCR7/IL-7 mRNA liposomes to edit CCR7+IL-7+ DCs in vivo, thus directly promoting Tscm differentiation within tumor-draining lymph nodes (TDLNs). The antigen-presenting CCR7+IL-7+ DCs migrate to the T-zone within TDLNs via CCR7-mediated signaling and secrete IL-7 to induce naive T cells to differentiate into Tscms. The antigens activate Tscms, promoting continuous Tscm self-renewal and effector T cell generation. The powerful antitumor effects have been observed in B16F10 and 4T1 tumor-bearing mice, and 80% of the mice exhibited suppressed distant tumor formation in the B16F10 prevention model. Overall, this research highlights the importance of Tscm abundance for antitumor immunotherapy and provides high clinical value for developing cancer vaccines.
SN - 2666-3791
ER -