4.8 Article

Injectable Liquid Crystal Formation System for Reshaping Tumor Immunosuppressive Microenvironment to Boost Antitumor Immunity: Postoperative Chemoimmunotherapy

期刊

SMALL
卷 16, 期 50, 页码 -

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202004905

关键词

cancer chemoimmunotherapy; in situ vaccine; liquid crystal formation system; postoperative treatment; tumor microenvironment

资金

  1. National Natural Science Foundation of China [81673374, 81872810]
  2. Program for HUST Academic Frontier Youth Team [2018QYTD13]
  3. Fundamental Research Funds for the Central Universities [2018KFYYXJJ019, 2019KFYRCPY049]
  4. Wuhan Science and Technology Plan for Applied Fundamental Research [2017060201010146]

向作者/读者索取更多资源

Exploring optimal strategies to improve patient outcome postoperatively is still under challenge. Cancer immunotherapy has great potential to prevent the postoperative tumor recurrence and metastasis, which could be further strengthened by re-education of tumor microenvironment (TME). Herein, a local and sustained drug delivery system of liquid crystal formation system (LCFS) co-loaded with doxorubicin (DOX) and resiquimod (R848) (D/R@LCFS) is reported to confer effective chemoimmunotherapy with reduced systematic toxicity. After local administration, D/R@LCFS turns tumor into in situ vaccine via DOX-triggered immunogenic cell death effect accompanied with immunostimulatory effect of R848. Meanwhile, combination treatment of D/R@LCFS facilitates the recruitment of effector CD8(+) T cells and the polarization of myeloid-derived suppressor cells and immunosuppressive type 2-polarized macrophages to tumoricidal antigen-presenting cells, favoring antigen-specific T cell immune response and inducing more immunogenic phenotypes in tumors. The generated in situ vaccine as well as reshaped TME by D/R@LCFS elicited systematic immune response and long term immune-memory effect in combination with immune checkpoint blockade to significantly prevent postoperative B16F10 or 4T1 tumor recurrence and metastasis. Therefore, this combination strategy of spatiotemporal TME modulation is expected to provide a clinical available option for effective postoperative chemoimmunotherapy.

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