Cationic polysaccharide sperminepullulan drives tumor associated macrophage towards

Cationic polysaccharide sperminepullulan drives tumor associated macrophage towards M 1 phenotype to inhibit tumor progression Int J Biol Macromol. 2019 Feb 15; 123: 1012 -1019. doi: 10. 1016/j. ijbiomac. 2018. 11. 089. Epub 2018 Nov 13 Xie L 1, Yang Y 1, Meng J 1, Wen T 1, Liu J 2, Xu H 3 1 IF : 3. 909 Speaker : JYUN-WEI YANG Advisor : Chi-Liang Chern

2 OUTLINE Introduction Materials & Methods Results Discussion

3 INTRODUCTION

4 What is tumor associated macrophage (TAM)? tissue growth and repair clear http: //www. anxinpiao. com/tupian/6 zmirsmnn http: //www. liangyihui. net/doc/36901

5 TAM surface marker TAMs(M 1) Marker : CD 80、CD 86 release : i. NOS、IFN-γ TLR、IRF、NF-κB activation Promote immunity : TNF-α�IL 12�IL 16 TAMs(M 2) Marker : CD 169、CD 206 Release : 　MMPs �TGF- β�EGF http: //ocapline. com/postview/id-22010

TAM is affected by ? 6 https: //www. hindawi. com/journals/bmri/2013/187204/fig 2/

7 What is Cationic polysaccharide spermine-pullulan(PS)? arginine PS structure Spermine modified pullulan cation

8 Cationic polysaccharide carriers for nucleic acids Vaccines Chemotherapeutics exhibit immune stimulatory effects

9 chitosan can promote dendritic cell maturation and enhancing Th 1 response , ethylenediamine-modified dextran can also stimulate Th 1 response and promote macrophages polarizing towards M 1.

10 Materials & Methods CCK-8 Lyso. Tracker Red DND-99 DAPI Flow Western q. RT-PCR https: //www. europeanpharmaceuticalreview. com/article/29 08/options-for-quantitative-analysis-by-real-time-pcr/ http: //www. folibio. com. tw/prod. Detail. asp? id=115

11 How to make FITC-PS? 100 mg PS 20 ml 0. 1 M sodium hydrogen carbonate 10 mg FITC 2 m. L DMSO stir in the dark for 24 hr DDW dialysis 3 days

12 Animal experiments Subcutaneous injection BALB / c mice 1× 10 6 4 T 1 cell Sick mice http: //www. biolasco. com. tw/index. php/tw/2014 -03 -2615 -23 -34/2014 -01 -16 -10 -41 -51/2014 -02 -17 -14 -49 -59

13 Results

14 Cell survival PS does not affect cell survival. FITC-PS

15 PS was took up by macrophages and located in lysosomes DAPI FITC DAPI Lyso. Tracker Red DND-99

16 PS drove M 0 or M 2 macrophages towards M 1 phenotype TNF-α ↑ i. NOS ↑ CD 206 ↓

17 the impact of IL-4

18 TNF-α ↑ i. NOS ↑ CD 206 ↓

19

20 PS activated immunological signaling proteins

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22 tumor progression and metastasis

23 Liver and lung lesions after treatment in mice

24 TAM phenotypic changes

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26 Tumor killing ability of T cells

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28 Conclusion M 2 PS M 1 T cell ↑ M 0 Effectively alleviate the immunosuppressive tumor microenvironment.

29 Thank you for attention