The immunosuppressive tumor microenvironment limits the application of adoptive immunotherapy for solid
tumors.
Hypoxia is closely associated with the formation of the immunosuppressive tumor microenvironment.
Hypoxia-inducible factor-1 (HIF-1) is an
oxygen-sensitive transcriptional activator that drives the transcription of several immunosuppressive molecules. In addition, previous studies confirmed that
rhein downregulated the expression of HIF-1α, a subunit of HIF-1, in
pancreatic cancer cells. The present study established correlations between
mRNA expression levels of HIF-1α and six immunosuppressive molecules in
colorectal cancer (CRC) tissue samples. This study examined the effect of
rhein on the expression levels of HIF-1α and six immunosuppressive molecules in CRC cell lines under hypoxic conditions by western blot analysis and reverse transcription-quantitative polymerase chain reaction. This study demonstrated that
rhein downregulated the expression of HIF-1α and immunosuppressive molecules in CRC cells under hypoxic conditions. In addition, the present study analyzed the cytotoxicity of peripheral blood lymphocytes in vitro using a non-toxic cytotoxicity assay. This study demonstrated that in vitro,
rhein enhanced the cytotoxicity of effector lymphocytes toward
tumor cells under hypoxic conditions, and therefore
rhein may be used in combination with effector lymphocytes for the treatment of CRC.