PFC@O-2 Targets HIF-1 alpha to Reverse the Immunosuppressive TME in OSCC

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-1 alpha 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.

Automated summary

Hypoxia in solid tumors affects tumor therapy, but targeting the hypoxic tumor microenvironment shows promise. In this study, a drug carrier was developed to alleviate hypoxia and inhibit the growth of oral squamous cell carcinoma (OSCC).