Together, these preclinical results demonstrated that high expression of SPHK1 has the potential to reverse resistance to anti-PD-1 mAb therapy induced by upregulated PD-L1 expression in tumors and that the SPHK1-MTA3 axis could serve as a potential biomarker for the prognosis of melanoma patients receiving anti-PD-1 immunotherapies. The gene discussed is SPHK1; the disease is melanoma.