PMID- 24841535 OWN - NLM STAT- MEDLINE DCOM- 20141110 LR - 20211021 IS - 1432-0851 (Electronic) IS - 0340-7004 (Print) IS - 0340-7004 (Linking) VI - 63 IP - 8 DP - 2014 Aug TI - Murine Th9 cells promote the survival of myeloid dendritic cells in cancer immunotherapy. PG - 835-45 LID - 10.1007/s00262-014-1557-4 [doi] AB - Dendritic cells (DCs) are professional antigen-presenting cells to initiate immune responses, and DC survival time is important for affecting the strength of T-cell responses. Interleukin (IL)-9-producing T-helper (Th)-9 cells play an important role in anti-tumor immunity. However, it is unclear how Th9 cells communicate with DCs. In this study, we investigated whether murine Th9 cells affected the survival of myeloid DCs. DCs derived from bone marrow of C57BL/6 mice were cocultured with Th9 cells from OT-II mice using transwell, and the survival of DCs was examined. DCs cocultured with Th9 cells had longer survival and fewer apoptotic cells than DCs cultured alone in vitro. In melanoma B16-OVA tumor-bearing mice, DCs conditioned by Th9 cells lived longer and induced stronger anti-tumor response than control DCs did in vivo. Mechanistic studies revealed that IL-3 but not IL-9 secreted by Th9 cells was responsible for the prolonged survival of DCs. IL-3 upregulated the expression of anti-apoptotic protein Bcl-xL and activated p38, ERK and STAT5 signaling pathways in DCs. Taken together, our data provide the first evidence that Th9 cells can promote the survival of DCs through IL-3, and will be helpful for designing Th9 cell immunotherapy and more effective DC vaccine for human cancers. FAU - Park, Jungsun AU - Park J AD - Department of Lymphoma and Myeloma, Division of Cancer Medicine, and Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Li, Haiyan AU - Li H FAU - Zhang, Mingjun AU - Zhang M FAU - Lu, Yong AU - Lu Y FAU - Hong, Bangxing AU - Hong B FAU - Zheng, Yuhuan AU - Zheng Y FAU - He, Jin AU - He J FAU - Yang, Jing AU - Yang J FAU - Qian, Jianfei AU - Qian J FAU - Yi, Qing AU - Yi Q LA - eng GR - R01 CA96569/CA/NCI NIH HHS/United States GR - P50 CA142509/CA/NCI NIH HHS/United States GR - R01 CA138398/CA/NCI NIH HHS/United States GR - R01 CA138402/CA/NCI NIH HHS/United States GR - R01 CA096569/CA/NCI NIH HHS/United States GR - R01 CA163881/CA/NCI NIH HHS/United States GR - R01 CA103978/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140520 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Interleukin-3) RN - 0 (Interleukin-9) SB - IM MH - Animals MH - Cell Communication/immunology MH - Cell Differentiation/immunology MH - Cell Survival/immunology MH - Coculture Techniques MH - Dendritic Cells/cytology/*immunology MH - Humans MH - Immunotherapy, Adoptive/*methods MH - Interleukin-3/biosynthesis/immunology MH - Interleukin-9/*immunology MH - Male MH - Melanoma, Experimental/immunology/*therapy MH - Mice MH - Mice, Inbred C57BL MH - Signal Transduction MH - T-Lymphocytes, Helper-Inducer/cytology/*immunology PMC - PMC4200484 MID - NIHMS597092 COIS- The authors declare no competing financial interests. EDAT- 2014/05/21 06:00 MHDA- 2014/11/11 06:00 PMCR- 2014/05/20 CRDT- 2014/05/21 06:00 PHST- 2013/10/28 00:00 [received] PHST- 2014/04/24 00:00 [accepted] PHST- 2014/05/21 06:00 [entrez] PHST- 2014/05/21 06:00 [pubmed] PHST- 2014/11/11 06:00 [medline] PHST- 2014/05/20 00:00 [pmc-release] AID - 1557 [pii] AID - 10.1007/s00262-014-1557-4 [doi] PST - ppublish SO - Cancer Immunol Immunother. 2014 Aug;63(8):835-45. doi: 10.1007/s00262-014-1557-4. Epub 2014 May 20.