The S1P-ALOX15 signaling mediated TAMs was supported by the results: 1) the recruited myeloid cells contributed to tumor-infiltrated macrophages which showed M2 phenotype with high level of 12/15-LOX; 2) S1P induced up-regulation of TAMs markers were significantly attenuated by either S1PR inhibitors or ALOX15 inhibitor; and 3) significant tumor regression in the 12/15-LOX−/− mice with obesity-lymphoma was found in association with less-infiltration of M2-macrophages/TAMs. The gene discussed is LOX; the disease is obesity due to melanocortin 4 receptor deficiency.