PMID- 32655564 OWN - NLM STAT- MEDLINE DCOM- 20210405 LR - 20211204 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - The Superior Ability of Human BDCA3(+) (CD141(+)) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells. PG - 1267 LID - 10.3389/fimmu.2020.01267 [doi] LID - 1267 AB - Dendritic cells (DCs) play a key role in initiating and regulating the immune responses to pathogens, self-antigens, and cancers. Human blood DCs comprise a family of different subsets: plasmacytoid DCs (pDCs) and CD16(+), CD1c/BDCA1(+), and BDCA3(+) (CD141(+)) myeloid DCs and possess different phenotypes and functional characteristics. Lung cancer is the most common cancer, with the highest morbidity and mortality in the world. However, which DC subset plays a leading role in the lung cancer immune responses is unclear. We reanalyzed C-type lectin domain family 9 member A (CLEC9A) and CD141 (THBD) gene expression profiles from the Cancer Genome Atlas (TCGA) database and performed the Kaplan-Meier survival analysis of overall survival for several cancers according to their expression levels. Next, we investigated the capacities of five human blood DC subsets to stimulate T cell proliferation and capture, process and (cross-) present tumor antigen. Human BDCA3(+) (CD141(+)) DCs have a superior capacity to stimulate allogeneic CD4(+)T cells proliferation and induce superior Th1 response compared with other DC subsets. Interestingly, toll-like receptor (TLR) agonists have little effect on DCs to induce the proliferation of naive CD4(+) T cells, but contribute to their differentiation. Importantly, BDCA3(+) (CD141(+)) DCs possess the most potent ability to cross-present human tumor antigen after their uptake of necrotic lung cancer cells despite their lower antigen uptake. These findings suggest that human BDCA3(+) (CD141(+)) DCs are critical mediators of cytotoxic T lymphocyte responses against EGFR-positive lung cancer. Therefore, our findings may provide theoretical basis for the development of DC-based antitumor vaccines. CI - Copyright (c) 2020 Gu, Zhang, Ma, Liu, Li, Hu, Yang, Liang, Zeng, Wang and Liu. FAU - Gu, Fei-Fei AU - Gu FF AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Kai AU - Zhang K AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Ma, Li-Li AU - Ma LL AD - Department of Oncology, Wuhan Brain Hospital, Wuhan, China. FAU - Liu, Yang-Yang AU - Liu YY AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Li, Chang AU - Li C AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Hu, Yue AU - Hu Y AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Yang, Qi-Fan AU - Yang QF AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Liang, Jin-Yan AU - Liang JY AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zeng, Yu-Lan AU - Zeng YL AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Wang, Yan AU - Wang Y AD - Analysis and Testing Center, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China. FAU - Liu, Li AU - Liu L AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200619 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antigens, Neoplasm) RN - 0 (Antigens, Surface) RN - 0 (THBD protein, human) RN - 0 (Thrombomodulin) SB - IM MH - Antigens, Neoplasm/*immunology MH - Antigens, Surface/immunology MH - Cells, Cultured MH - Cross-Priming/*immunology MH - Dendritic Cells/*immunology MH - Humans MH - Lung Neoplasms/*immunology MH - Necrosis/immunology MH - T-Lymphocytes, Cytotoxic/*immunology MH - Thrombomodulin PMC - PMC7325999 OTO - NOTNLM OT - EGFR OT - TLR OT - antitumor vaccine OT - cytotoxic T lymphocyte OT - dendritic cell OT - lung cancer EDAT- 2020/07/14 06:00 MHDA- 2021/04/07 06:00 PMCR- 2020/01/01 CRDT- 2020/07/14 06:00 PHST- 2019/11/04 00:00 [received] PHST- 2020/05/19 00:00 [accepted] PHST- 2020/07/14 06:00 [entrez] PHST- 2020/07/14 06:00 [pubmed] PHST- 2021/04/07 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.01267 [doi] PST - epublish SO - Front Immunol. 2020 Jun 19;11:1267. doi: 10.3389/fimmu.2020.01267. eCollection 2020.