Natural Killer Cell Dysfunction in Obese Patients with Breast Cancer: A Review of a Triad and Its Implications

Figure 1

Triad of obesity, natural killer cells, and breast cancer. Typically, natural killer (NK) cells release perforin and granzyme B, molecules that cause cytotoxicity and induce apoptosis of breast cancer (BC) cells. Additionally, NK cells stimulate the expression of CD54, PD-L1, and MHC class I molecules on cancer stem cells, which inhibit the metastasis and proliferation of breast cancer cells. In turn, hypoxic environment of breast cancer cells and secreted TGF-β by stromal cells in the tumor microenvironment (TME) cause a reduction in the activating receptors (NKG2D and NKp30) as well as the NK cell function: IFN-γ production and cytotoxicity via perforin and granzyme B release. Similarly, adipose tissue causes a reduction in TRAIL, NKp30, and NKG2D expression in obese patients. Lipid droplet accumulation in NK cells leads to a reduction in cytokine release such as IFN-γ. Controversial data were reported regarding the count and status of NK cells in obese individuals. On the other arm, adipose tissue secretes IL-6, PGE2, TNF-α, and adipokines such as leptin which trigger the proliferation of breast cancer cells via the MAPK and mTOR pathways.