Further, we discuss the role of chemotherapy-induced TME changes in modulating TNBC immune response and tumor progression, with a focus on HMGB1, exosomes, and sphingosine-1-phosphate (S1P)/sphingosine kinase 1 (SPHK1)/S1PR1, an axis whose therapeutic modulation may result in neoteric combination therapy for TNBC patients. This evidence concerns the gene SPHK1 and neoplasm.