Thus, we suggest how the combined therapeutic approaches specifically targeting peritumoral adipose tissue mediators (i.e., Ob/ObR signaling) and removing the immunosuppressed activities of macrophages through the use of neutralizing PD-L1/PD-1 and ARG 1 antibodies may prospectively become extremely promising in the individualized assessed treatment of overweight/obese breast cancer patients. The gene discussed is CD274; the disease is breast cancer.