title: Re-polarizing Myeloid-derived Suppressor Cells (MDSCs) with Cationic Polymers for Cancer Immunotherapy.
abstract: Our evolving understandings of cell-material interactions provide insights for using polymers to modulate cell behaviour that may lead to therapeutic applications. It is known that in certain cancers, myeloid-derived suppressor cells (MDSCs) play vital roles in promoting tumour progression, chiefly because of their 'alternatively activated' (or M2) phenotype that orchestrates immunosuppression. In this study, we demonstrated that two cationic polymers - cationic dextran (C-dextran) and polyethyleneimine (PEI) - could directly remodel these cells into an anti-tumour, 'classically activated' (or M1) phenotype, thereby stimulating these cells to express tumouricidal cytokines, reactivating the T cell functions, and prolonging the lifespan of the mice model. Our investigations with knock-out mice further indicate that the functions of these cationic polymers require the involvement of toll-like receptor 4-mediated signalling. Taken together, our study suggests that these cationic polymers can effectively and directly re-polarize MDSCs from an immunosuppressive characteristic to an anti-tumour phenotype, leading to successful restoration of immune surveillance in the tumour microenvironment and elimination of tumour cells. Our findings may have immediate impact on further development of polymer-based therapeutics for cancer immunotherapy.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China.
authors.forename: Guangxing
authors.initials: G
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR.
authors.forename: Chunming
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China.|Jiangsu Provincial Laboratory for Nano-Technology, Nanjing University, Nanjing, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002412:Cations / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism*; D007167:Immunotherapy / Q000379:methods*; D015674:Mammary Neoplasms, Animal / Q000628:therapy*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects* / Q000502:physiology*; D011094:Polyethyleneimine / Q000378:metabolism*; D016019:Survival Analysis; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D002412:Cations; D003911:Dextrans; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D011094:Polyethyleneimine