S1PR1 and cancer: IL-6/JAK (Janus Kinase)/STAT3 signal transduction, a crucial signaling pathway that is aberrantly hyperactivated in cancer cells or under chronic inflammation conditions, can be directly activated by S1PR1 and feedback onto S1PR1 to prevent its phosphorylation in CD4+ T cells, leading to enhanced Th17 polarization (78, 79).