Authors
Yiting Wei, Jing Chen, Yunpeng Zhang, Yueming Liu, Fengjiao Zhu, Xuru Wang, Xiaohe Zhou, Chengdong Wu, Wenqi Zhang, Jinpeng Chen, Yuchen Zhang, Ning Pan, Kang Chen, Shiya Zheng, Chunguang Yan, Ling Liu, Lixin Wang
Published in
Cancer research. Jun 15, 2026. Epub Jun 15, 2026.
Abstract
Chemotherapy induces cancer cell apoptosis and the release of apoptotic bodies (ABs) that are poorly immunogenic or immunosuppressive, creating a major barrier to the success of co-administered or second-line immunotherapies. Here, we found reduced circulating levels of thymosin alpha-1 (Tα-1), a key endogenous peptide hormone with immunomodulatory activity, after chemotherapy treatment in patients with multiple types of cancer and mice bearing established tumors. Tα-1 bound to tumor ABs and interacted with AB-borne microRNAs, including miR146a-5p, following phagocytosis of ABs into the endolysosomal compartment of dendritic cells (DCs). The interaction with Tα-1 protected miR146a-5p from lysosomal RNase A-mediated degradation, allowing miR146a-5p-mediated activation of Toll-like receptor 7 (TLR7) that licenses DC maturation, migration to tumor-draining lymph nodes, and presentation of tumor antigens to activate tumor-specific CD8+ T cells. Therapeutic Tα-1 supplementation produced strong synergy with chemotherapy to control established tumors in mice with high miR146a-5p expression in a TLR7-dependent manner. These findings establish Tα-1 as a pivotal endogenous microRNA chaperone that unlocks a critical limiting step of DC licensing, empowering robust antitumor immunity after chemotherapy.
PMID:
42295795
Bibliographic data and abstract were imported from PubMed on 15 Jun 2026.
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