树突状细胞与肿瘤免疫研究进展.pptx

1、Dendritc Cells,李雨箫 Li Yuxiao 协和10级 pumc2010 学号 student ID：201001028,Development,Myeloid DC Plasmacytoid DC,#NATURE REVIEWS | IMMUNOLOGY VOLUME 12 | APRIL 2012,Antigen presentation,Kuby Immunology 6th edition,Endogenous antigen,Kuby Immunology 6th edition,Exogenous antigen,MHC II Invariant chain CLIP

2、 (Class II-associated Invariant Chain Peptide) HLADM和HLADO,Kuby Immunology 6th edition,Activation of T cell,Signal1 Signal2 Cytokines,Kuby Immunology 6th edition,Dendritic Cells,Not only antigen presentation!,Induce innate immunity,IMMUNOBIOLOGY OF DENDRITIC CELLS Jacques Banchereau et al. Annu. Rev

3、. Immunol. 2000. 18:767811,Immune tolerance,#Journal of Cancer Molecules 2(6): 213-215, 2006.,Tumor microenvironment and DCs,Hot Issue,Convert differentDCs to macrophage-like DCs,# Immunol. 2013 Nov 25;4:403,CD14+ macrophage-like DCs,Poor T cell stimulatory abililites T cell suppressive activity Cal

4、led M2-type macrophages CD1c,# Immunol. 2013 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 for Th1 induction Carry low levels of co-stimulatory molecules,Convert monocyte to macrophage-like DCs,IL-10, IL-6,

5、 or PGE2,# Blood.2011 November 17;118(20): 54985505.,Convert fully differentiatedDCs to macrophage-like DCs,IL-10,# J Invest Dermatol. 2011 Feb;131(2):418-25. doi: 10.1038.,Convert fully differentiatedDCs to macrophage-like DCs,IL-10,# Int J Gynecol Cancer 2009;19: 1487Y1493,Convert fully differenti

6、atedDCs to macrophage-like DCs,IL-10,# Int J Gynecol Cancer 2009;19: 1487Y1493,Convert differentDCs to macrophage-like DCs,# Immunol. 2013 Nov 25;4:403,Macrophage-like DCs share some striking traits,Release of immunosuppressive IL-10 (high) Expression of HIF1a, TGF-, VEGFA, MMP3, MMP9, IL-8, and TNF

7、a Contribute to tumor-promoting processes Endothelial cell migration and proliferation Tumor growth and invasion,Changes that occur in myeloid cells in cancer,#NATURE REVIEWS | IMMUNOLOGY VOLUME 12 | APRIL 2012,SIGNAL TRANSDUCTION PATHWAYS ACTING AS MASTERSWITCHES OF TUMOR-INDUCED DC SUPPRESSION,JAK

8、2/STAT3 signaling pathway,JAK/STAT signaling pathway,Activated by interferon, interleukin, growth factors JAK：Janus Kinase STAT：Signal transducers and activators of transcription,#Science 296 (5573): 16535. doi:10.1126/science.1071545,JAK2/STAT3 signaling pathway,#Nat Rev Cancer. 2009 Nov;9(11):798-

9、809. doi: 10.1038/nrc2734,INDIRECT EVIDENCE,Combined STAT3 and p38-MAPKinhibition was required,#OncoImmunology 1:5, 649658; august 2012,Combined STAT3 and p38-MAPKinhibition was required,#OncoImmunology 1:5, 649658; august 2012,DIRECT EVIDENCE！,THERAPEUTIC ACTIVATION,JAK2/STAT3 and/or p38-MAPK signa

10、ling interference Local immune potentiation DC-stimulatory agents GM-CSF, IL4,Local immune potentiation,#BLOOD, 12 APRIL 2012， VOLUME 119, NUMBER 15,Local immune potentiation,GM-CSF, IL4 Stimulate T, B cells,#J Immunol 2012; 189:5223-5229,Local immune potentiation,GM-CSF, IL4 More antibody,#J Immuno

11、l 2012; 189:5223-5229,Local immune potentiation,TLRagonists, such as LPS CpG oligodeoxynucleotides,Reference,van de Ven R, Lindenberg 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 immu

12、nology, 2013, 4. Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cellsJ. Annual review of immunology, 2000, 18(1): 767-811. Liu K J. Dendritic cell, toll-like receptor, and the immune systemJ. J Cancer Mol, 2006, 2: 213. Obermajer N, Muthuswamy R, Lesnock J, et al. Positive feedbac

13、k between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cellsJ. Blood, 2011, 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

14、macrophage-like phenotypeJ. Journal of Investigative Dermatology, 2010, 131(2): 418-425.,Chen F,HouM,Ye F, LvW,Xie X. Ovarian cancer cells induce peripheralmature dendritic cells to differentiate into macrophagelike cells in vitro. Int J Gynecol Cancer (2009) 19:148793. doi:10.1111/IGC.0b013e3181bb7

15、0c6 Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3J. Nature Reviews Cancer, 2009, 9(11): 798-809. Oosterhoff D, Lougheed S, van de Ven R, et al. Tumor-mediated inhibition of human dendritic cell differentiation and function is consistently counteracted b

16、y combined p38 MAPK and STAT3 inhibitionJ. Oncoimmunology, 2012, 1(5): 649-658. Vuylsteke RJCLM, Molenkamp BG, van Leeuwen PAM, Meijer S, Wijnands PGJTB, Haanen JBAG, et al. Tumor-specic CD8+ T cell reactivity in the sentinel lymph node of GM-CSF-treated stage I melanoma patients is associated with

17、high myeloid dendritic cell content. Clin Cancer Res (2006) 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. Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inammation. J Exp Med (2012) 209:93545. doi:10.1084/jem.20112583 Banchereau J, Thompson-Snipes L, Zurawski S, Blanck J-P, Cao Y, Clayton S, et al. The differential production of cytokines by human Langerhans cells and dermal CD14(+) DCs controls CTL priming. Blood (2012)