PFC@O 2 Targets HIF-1α to Reverse the Immunosuppressive TME in OSCC.
Zhou LanKe-Long ZouHao CuiHao ChenYu-Yue ZhaoGuang-Tao YuPublished in: Journal of clinical medicine (2023)
As a typical hallmark of solid tumors, hypoxia affects the effects of tumor radiotherapy, chemotherapy, and photodynamic therapy. Therefore, targeting the hypoxic tumor microenvironment (TME) is a promising treatment strategy for cancer therapy. Here, we prepared an Albumin Human Serum (HSA)-coated perfluorocarbon (PFC) carrying oxygen (PFC@O 2 ) to minimize OSCC hypoxia. The results showed that PFC@O 2 significantly downregulated the expression of HIF-1α and the number of M2-like macrophages in vitro. Furthermore, PFC@O 2 effectively inhibited the growth of oral squamous cell carcinoma (OSCC) and reduced the proportion of negative immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs) and M2-like macrophages of TME in a 4-nitroquinoline N-oxide (4NQO)-induced mouse model. Conversely, the infiltration of CD4 + and CD8 + T cells was significantly increased in TME, suggesting that the anti-tumor immune response was enhanced. However, we also found that hypoxia-relative genes expression was positively correlated with CD68 + /CD163 + TAMs in human tissue specimens. In summary, PFC@O 2 could effectively inhibit the progression of OSCC by alleviating hypoxia, which provides a practical basis for gas therapy and gas synergistic therapy for OSCC.
Keyphrases
- endothelial cells
- cancer therapy
- high glucose
- induced apoptosis
- photodynamic therapy
- poor prognosis
- immune response
- cell cycle arrest
- mouse model
- drug delivery
- early stage
- radiation therapy
- locally advanced
- oxidative stress
- room temperature
- stem cells
- squamous cell carcinoma
- long non coding rna
- signaling pathway
- genome wide
- radiation induced
- ionic liquid
- inflammatory response
- induced pluripotent stem cells
- gene expression
- toll like receptor
- transcription factor
- replacement therapy
- dendritic cells
- combination therapy
- rectal cancer
- carbon dioxide
- pluripotent stem cells
- stress induced