These observations are supported by our findings displaying a correlation between SPHK1 amounts and increased tumor-supporting TAMs in GB patients, thus pointing towards a pivotal role played by S1P in the glioma–microenvironment crosstalk and highlighting the possibility of targeting the SPHK–S1P–S1PR axis across these two compartments as a novel strategy in glioma therapy. This evidence concerns the gene SPHK1 and central nervous system cancer.