Normalizing the Immune Macroenvironment via Debulking Surgery to Strengthen Tumor Nanovaccine Efficacy and Eliminate Metastasis

Nana Ma, Zhiqiang Chen, Guangna Liu, Yale Yue, Yao Li, Keman Cheng, Xiaotu Ma, Qingqing Feng, Jie Liang, Tianjiao Zhang, Xiaoyu Gao, Xinwei Wang, Xinjing Guo, Fei Zhu, Guangjun Nie, Xiao Zhao

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

In tumor nanovaccines, nanocarriers enhance the delivery of tumor antigens to antigen-presenting cells (APCs), thereby ensuring the robust activation of tumor antigen-specific effector T-cells to kill tumor cells. Through employment of their high immunogenicity and nanosize, we have developed a “Plug-and-Display” delivery platform on the basis of bacterial outer membrane vesicles (OMVs) for tumor nanovaccines (NanoVac), which can rapidly display different tumor antigens and efficiently eliminate lung metastases of melanoma. In this study, we first upgraded the NanoVac to increase their antigen display efficiency. However, we found that the presence of a subcutaneous xenograft seriously hampered the efficiency of NanoVac to eliminate lung metastases, with the subcutaneous xenograft mimicking the primary tumor burden in clinical practice. The primary tumor secreted significant amounts of granulocyte colony-stimulating factor (G-CSF) and altered the epigenetic features of granulocyte monocyte precursor cells (GMPs) in the bone marrow, thus disrupting systemic immunity, particularly the function of APCs, and ultimately resulting in NanoVac failure to affect metastases. These changes in the systemic immune macroenvironment were plastic, and debulking surgery of primary tumor resection reversed the dysfunction of APCs and failure of NanoVac. These results demonstrate that, in addition to the formulation design of the tumor nanovaccines themselves, the systemic immune macroenvironment incapacitated by tumor development is another key factor that cannot be ignored to affect the efficiency of tumor nanovaccines, and the combination of primary tumor resection with NanoVac is a promising radical treatment for widely metastatic tumors.

Original languageEnglish (US)
Pages (from-to)437-452
Number of pages16
JournalACS Nano
Volume17
Issue number1
DOIs
StatePublished - Jan 10 2023

Keywords

  • G-CSF
  • antigen presentation
  • debulking surgery
  • metastasis elimination
  • systemic immunity
  • tumor nanovaccines

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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