PMID- 32468023 OWN - NLM STAT- MEDLINE DCOM- 20210505 LR - 20210914 IS - 1791-2423 (Electronic) IS - 1019-6439 (Linking) VI - 57 IP - 2 DP - 2020 Aug TI - Silencing IDO2 in dendritic cells: A novel strategy to strengthen cancer immunotherapy in a murine lung cancer model. PG - 587-597 LID - 10.3892/ijo.2020.5073 [doi] AB - While dendritic cell (DC)‑based immunotherapy has achieved satisfactory results in animal models, its effects were not satisfactory as initially expected in clinical applications, despite the safety and varying degrees of effectiveness in various types of cancer. Improving the efficacy of the DC‑based vaccine is essential for cancer immunotherapy. The present study aimed to investigate methods with which to amplify and enhance the antitumor immune response of a DC‑based tumor vaccine by silencing the expression of indoleamine 2,3‑dioxygenase 2 (IDO2), a tryptophan rate‑limiting metabolic enzyme in DCs. In vitro experiments revealed that the silencing of IDO2 in DCs did not affect the differentiation of DCs, whereas it increased their expression of costimulatory molecules following stimulation with tumor necrosis factor (TNF)‑alpha and tumor lysate from Lewis lung cancer (LLC) cells. In a mixed co‑culture system, the IDO2‑silenced DCs promoted the proliferation of T‑cells and reduced the induction of regulatory T‑cells (Tregs). Further in vivo experiments revealed that the silencing of IDO2 in DCs markedly suppressed the growth of tumor cells. Moreover, treatment with the IDO2‑silenced DC‑based cancer vaccine enhanced cytotoxic T lymphocyte activity, whereas it decreased T‑cell apoptosis and the percentage of CD4+CD25+Foxp3+ Tregs. On the whole, the present study provides evidence that the silencing of the tryptophan rate‑limiting metabolic enzyme, IDO2, has the potential to enhance the efficacy of DC‑based cancer immunotherapy. FAU - Liu, Yanling AU - Liu Y AD - Medical Laboratory, Jiangxi University of Technology, Nanchang, Jiangxi 330098, P.R. China. FAU - Xu, Ping AU - Xu P AD - Medical Laboratory, Jiangxi University of Technology, Nanchang, Jiangxi 330098, P.R. China. FAU - Liu, Huan AU - Liu H AD - Medical Laboratory, Jiangxi University of Technology, Nanchang, Jiangxi 330098, P.R. China. FAU - Fang, Chunjuan AU - Fang C AD - Medical Laboratory, Jiangxi University of Technology, Nanchang, Jiangxi 330098, P.R. China. FAU - Guo, Haihe AU - Guo H AD - Medical Laboratory, Jiangxi University of Technology, Nanchang, Jiangxi 330098, P.R. China. FAU - Chen, Xiaoyan AU - Chen X AD - Medical Laboratory, Jiangxi University of Technology, Nanchang, Jiangxi 330098, P.R. China. FAU - Tan, Manman AU - Tan M AD - Institute of Immunotherapy, Nanchang University and Jiangxi Academy of Medical Science, Nanchang, Jiangxi 330098, P.R. China. FAU - Zhang, Yujuan AU - Zhang Y AD - Institute of Immunotherapy, Nanchang University and Jiangxi Academy of Medical Science, Nanchang, Jiangxi 330098, P.R. China. FAU - Min, Weiping AU - Min W AD - Institute of Immunotherapy, Nanchang University and Jiangxi Academy of Medical Science, Nanchang, Jiangxi 330098, P.R. China. LA - eng PT - Journal Article DEP - 20200526 PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (Cancer Vaccines) RN - 0 (IDO2 protein, mouse) RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) RN - 0 (Tnf protein, mouse) RN - 0 (Tumor Necrosis Factor-alpha) RN - 8DUH1N11BX (Tryptophan) SB - IM MH - Animals MH - Cancer Vaccines/administration & dosage/*immunology MH - Carcinoma, Lewis Lung/genetics/immunology/pathology/*therapy MH - Cell Line, Tumor MH - Coculture Techniques MH - Dendritic Cells/*immunology/metabolism MH - Female MH - Immunotherapy/*methods MH - Indoleamine-Pyrrole 2,3,-Dioxygenase/*genetics/metabolism MH - Mice MH - RNA Interference MH - T-Lymphocytes, Cytotoxic/immunology MH - T-Lymphocytes, Regulatory/immunology MH - Tryptophan/metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - dendritic cells OT - siRNA OT - IDO2 OT - immunotherapy OT - lung cancer EDAT- 2020/05/30 06:00 MHDA- 2021/05/06 06:00 CRDT- 2020/05/30 06:00 PHST- 2019/11/19 00:00 [received] PHST- 2020/05/06 00:00 [accepted] PHST- 2020/05/30 06:00 [pubmed] PHST- 2021/05/06 06:00 [medline] PHST- 2020/05/30 06:00 [entrez] AID - 10.3892/ijo.2020.5073 [doi] PST - ppublish SO - Int J Oncol. 2020 Aug;57(2):587-597. doi: 10.3892/ijo.2020.5073. Epub 2020 May 26.