树突状细胞与肿瘤免疫研究进展ppt课件

1、Dendritc Cells李雨箫 Li Yuxiao协和10级 pumc2019学号 student ID：201901028本文档由医学百事通高端医生网专家制造本文档由医学百事通高端医生网专家制造免费咨询医生免费咨询医生12320bst;Development Myeloid DC Plasmacytoid DC#NATURE REVIEWS | IMMUNOLOGYVOLUME 12 | APRIL 2019;Dendritic cellsPresence of danger signalsAdaptive immunityAntigen presentationInnate immun

2、ityAbsence of danger signalsImmune tolerance;Dendritic cellsPresence of danger signalsAdaptive immunityAntigen presentationInnate immunityAbsence of danger signalsImmune tolerance;Antigen presentationKuby Immunology 6th edition;Endogenous antigenKuby Immunology 6th edition;Exogenous antigen MHC II I

3、nvariant chain CLIP (Class II-associated Invariant Chain Peptide) HLADM和HLADOKuby Immunology 6th edition;Activation of T cell Signal1 Signal2 CytokinesKuby Immunology 6th edition;Dendritic CellsNot only antigen presentation!;Dendritic cellsPresence of danger signalsAdaptive immunityAntigen presentat

4、ionInnate immunityAbsence of danger signalsImmune tolerance;Induce innate immunityIMMUNOBIOLOGY OF DENDRITIC CELLS Jacques Banchereau et al. Annu. Rev. Immunol. 2000. 18:767811;Dendritic cellsPresence of danger signalsAdaptive immunityAntigen presentationInnate immunityAbsence of danger signalsImmun

5、e tolerance;Immune tolerance#Journal of Cancer Molecules 2(6): 213-215, 2019.;Dendritic cellsPresence of danger signalsAdaptive immunityAntigen presentationInnate immunityAbsence of danger signalsImmune tolerance;Tumor microenvironment and DCsHot Issue;Convert differentDCs to macrophage-like DCs# Im

6、munol. 2019 Nov 25;4:403;CD14+ macrophage-like DCs Poor T cell stimulatory abililites T cell suppressive activity Called M2-type macrophages CD1c# Immunol. 2019 Nov 25;4:403;CD14+ macrophage-like DCs CD14+ DDC (dermal dendritic cell ) Poor inducers of allogeneic T cells Require high DC:T cell ratios

7、 for Th1 induction Carry low levels of co-stimulatory molecules;Convert monocyte to macrophage-like DCs IL-10, IL-6, or PGE2# Blood. 2019 November 17; 118(20): 54985505.;Convert fully differentiatedDCs to macrophage-like DCs IL-10# J Invest Dermatol. 2019 Feb;131(2):418-25. doi: 10.1038.;Convert ful

8、ly differentiatedDCs to macrophage-like DCs IL-10# Int J Gynecol Cancer 2021;19: 1487Y1493;Convert fully differentiatedDCs to macrophage-like DCs IL-10# Int J Gynecol Cancer 2021;19: 1487Y1493;Convert differentDCs to macrophage-like DCs # Immunol. 2019 Nov 25;4:403;Macrophage-like DCs share some str

9、iking traits Release of immunosuppressive IL-10 (high) Expression of HIF1a, TGF-, VEGFA, MMP3, MMP9, IL-8, and TNFa Contribute to tumor-promoting processes Endothelial cell migration and proliferation Tumor growth and invasion; Changes that occur in myeloid cells in cancer#NATURE REVIEWS | IMMUNOLOG

10、YVOLUME 12 | APRIL 2019;SIGNAL TRANSDUCTION PATHWAYS ACTING AS MASTERSWITCHES OF TUMOR-INDUCED DC SUPPRESSION;JAK2/STAT3 signaling pathway ;JAK/STAT signaling pathway Activated by interferon, interleukin, growth factors JAK：Janus Kinase STAT：Signal transducers and activators of transcription#Science

11、 296 (5573): 16535. doi:10.1126/science.1071545;JAK2/STAT3 signaling pathway #Nat Rev Cancer. 2021 Nov;9(11):798-809. doi: 10.1038/nrc2734INDIRECT EVIDENCE;Combined STAT3 and p38-MAPKinhibition was required#OncoImmunology 1:5, 649658; august 2019;Combined STAT3 and p38-MAPKinhibition was required#On

12、coImmunology 1:5, 649658; august 2019DIRECT EVIDENCE！;MonocyteImmature DCMature DCM2Macrophage-like DCIL-10pSTAT3p38IL-10IL-6PEG2pSTAT3IL-10IL-6PEG2IL-10IL-10, HIF1a, TGF-, VEGFA, MMP3, MMP9, IL-8, and TNFapSTAT3p38pSTAT3p38pSTAT3p38;THERAPEUTIC ACTIVATION JAK2/STAT3 and/or p38-MAPK signaling interf

13、erence Local immune potentiation DC-stimulatory agents GM-CSF, IL4;Local immune potentiation#BLOOD, 12 APRIL 2019， VOLUME 119, NUMBER 15;Local immune potentiation GM-CSF, IL4 Stimulate T, B cells #J Immunol 2019; 189:5223-5229;Local immune potentiation GM-CSF, IL4 More antibody#J Immunol 2019; 189:5

14、223-5229;Local immune potentiation TLR agonists, such as LPS CpG oligodeoxynucleotides;MonocyteImmature DCMature DCM2Macrophage-like DCIL-10pSTAT3p38IL-10IL-6PEG2pSTAT3IL-10IL-6PEG2IL-10IL-10, HIF1a, TGF-, VEGFA, MMP3, MMP9, IL-8, and TNFapSTAT3p38pSTAT3p38pSTAT3p38;Referencevan de Ven R, Lindenberg

15、 J J, Oosterhoff D, et al. Dendritic Cell Plasticity in Tumor-Conditioned Skin: CD14+ Cells at the Cross-Roads of Immune Activation and SuppressionJ. Frontiers in immunology, 2019, 4.Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cellsJ. Annual review of immunology, 2000, 18(1): 7

16、67-811.Liu K J. Dendritic cell, toll-like receptor, and the immune systemJ. J Cancer Mol, 2019, 2: 213.Obermajer N, Muthuswamy R, Lesnock J, et al. Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cellsJ. Blood, 2

17、019, 118(20): 5498-5505.Ouwehand K, Oosterhoff D, Breetveld M, et al. Irritant-induced migration of Langerhans cells coincides with an IL-10-dependent switch to a macrophage-like phenotypeJ. Journal of Investigative Dermatology, 2019, 131(2): 418-425.;Chen F,HouM,Ye F, LvW,Xie X. Ovarian cancer cell

18、s induce peripheralmature dendritic cells to differentiate into macrophagelike cells in vitro. Int J Gynecol Cancer (2021) 19:148793. doi:10.1111/IGC.0b013e3181bb70c6Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3J. Nature Reviews Cancer, 2021, 9(11): 798

19、-809.Oosterhoff D, Lougheed S, van de Ven R, et al. Tumor-mediated inhibition of human dendritic cell differentiation and function is consistently counteracted by combined p38 MAPK and STAT3 inhibitionJ. Oncoimmunology, 2019, 1(5): 649-658.Vuylsteke RJCLM, Molenkamp BG, van Leeuwen PAM, Meijer S, Wi

20、jnands PGJTB, Haanen JBAG, et al. Tumor-specific CD8+ T cell reactivity in the sentinel lymph node of GM-CSF-treated stage I melanoma patients is associated with high myeloid dendritic cell content. Clin Cancer Res (2019) 12:282633.doi:10.1158/1078-0432.CCR-05-2431;Chu C-C, Ali N, Karagiannis P, Di Meglio P, Skowera A, Napolitano L, et al.