PMID- 35803328 OWN - NLM STAT- MEDLINE DCOM- 20220920 LR - 20221019 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 349 DP - 2022 Sep TI - A therapeutic DC vaccine with maintained immunological activity exhibits robust anti-tumor efficacy. PG - 254-268 LID - S0168-3659(22)00401-1 [pii] LID - 10.1016/j.jconrel.2022.06.059 [doi] AB - Dendritic cells (DCs) vaccines are a major focus of future anti-tumor immunotherapy for their pivotal role in eliciting reactive tumor-specific T-cell responses. Tumor cell-mediated DCs (TC-DC) activation and tumor antigen-mediated DCs (TA-DC) activation are two conventional modes of DC vaccine construction in clinical studies. The former physiologically mimicks the tumor identification and rejection, significantly contributing to DC-based immune recognition and migration towards the complexed tumor microenvironment (TME). However, as immunosuppressive molecules may exist in TME, these TC-DC are generally characterized with aberrant lipid accumulation and inositol-requiring kinase 1alpha (IRE1alpha)-X-box binding protein 1 (XBP1) hyperactivation, which is provoked by overwhelming oxidative stress and endoplasmic reticulum (ER) stress, resulting in TC-DC malfunction. Oppositely, without contacting immunosuppressive TME, TA-DC vaccines perform better in T-cell priming and lymph nodes (LNs) homing, but are relatively weak in TME infiltration and identification. Herein, we prepared a KIRA6-loaded alpha-Tocopherol nanoemulsion (KT-NE), which simultaneously ameliorated oxidative stress and ER stress in the dysfunctional lipid-laden TC-DC. The TC-DC treated by KT-NE could maintain immunological activity, simultaneously, exhibited satisfactory chemotaxis towards LNs and tumor sites in vivo, and effectively suppressed malignant progression by unleashing activated tumor-reactive T cells. This study generated a new DC-vaccine that owned puissant aptitude to identify complicated TME as well as robust immunological activity to boost T-cell initiation, which may provide some insights into the design and application of DC-vaccines for clinical application. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Lu, Yichao AU - Lu Y AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Shi, Yingying AU - Shi Y AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Liu, Yu AU - Liu Y AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Luo, Zhenyu AU - Luo Z AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Zhang, Junlei AU - Zhang J AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Jiang, Mengshi AU - Jiang M AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Li, Xiang AU - Li X AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Liu, Xu AU - Liu X AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Guo, Xuemeng AU - Guo X AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Qin, Bing AU - Qin B AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Yin, Hang AU - Yin H AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Du, Yongzhong AU - Du Y AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Qiu, Yunqing AU - Qiu Y AD - Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310000, PR China. FAU - Lou, Yan AU - Lou Y AD - Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310000, PR China. FAU - Guan, Guannan AU - Guan G AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - Luo, Lihua AU - Luo L AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. FAU - You, Jian AU - You J AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. Electronic address: youjiandoc@zju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220709 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (Lipids) RN - 0 (X-Box Binding Protein 1) RN - 4L6452S749 (Inositol) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 3.1.- (Endoribonucleases) RN - H4N855PNZ1 (alpha-Tocopherol) SB - IM MH - Antigens, Neoplasm MH - *Cancer Vaccines MH - Dendritic Cells MH - Endoribonucleases MH - Humans MH - Inositol MH - Lipids MH - *Neoplasms/therapy MH - Protein Serine-Threonine Kinases MH - Tumor Microenvironment MH - X-Box Binding Protein 1 MH - alpha-Tocopherol OTO - NOTNLM OT - Anti-tumor efficacy OT - DC vaccine OT - Maintained immunological activity OT - Oxidative stress OT - XBP1 COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/07/09 06:00 MHDA- 2022/09/21 06:00 CRDT- 2022/07/08 19:23 PHST- 2022/04/15 00:00 [received] PHST- 2022/06/28 00:00 [revised] PHST- 2022/06/29 00:00 [accepted] PHST- 2022/07/09 06:00 [pubmed] PHST- 2022/09/21 06:00 [medline] PHST- 2022/07/08 19:23 [entrez] AID - S0168-3659(22)00401-1 [pii] AID - 10.1016/j.jconrel.2022.06.059 [doi] PST - ppublish SO - J Control Release. 2022 Sep;349:254-268. doi: 10.1016/j.jconrel.2022.06.059. Epub 2022 Jul 9.