樹突狀細胞與腫瘤免疫研究進展ppt課件

1、Dendritc Cells李雨簫 Li Yuxiao協(xié)和10級 pumc2019學(xué)號 student ID：201901028本文檔由醫(yī)學(xué)百事通高端醫(yī)生網(wǎng)專家制造本文檔由醫(yī)學(xué)百事通高端醫(yī)生網(wǎng)專家制造免費咨詢醫(yī)生免費咨詢醫(yī)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.