Suppression of CD56^bright NK cells in breast cancer patients is associated with the PD-1 and TGF-βRII expression

Background: Natural killer (NK) cells, as professional cytotoxic cells, play a key role against cancer in the early and metastatic stages. Their functional defects are highly associated with the initiation or progression of breast cancer (BC). Here, we investigated the phenotypic characterization of NK cells in 26 newly diagnosed BC patients in comparison to 12 healthy counterparts.

Methods: Expression of CXCR3 and PD-1, and also NKG2D, and TGF-βRII were studied on CD56^dim and CD56^bright NK cells from fresh peripheral blood (PB) samples using flow cytometry. The plasma levels of IFN-γ and soluble MIC-A levels were also assessed by ELISA.

Results: Both CD56^dim and CD56^bright NK subtypes showed lower CXCR3 and NKG2D expression in BC patients than healthy subjects. Furthermore, patients' CD56^bright NK cells significantly showed higher expression levels of TGF-βRII and PD-1. Interestingly, increased concentration of MIC-A level in plasma of BC patients was associated with the higher TGF-βRII and PD-1 expression in all NK cells, while the plasma level of IFN-γ was associated with the lower TGF-βRII expression on CD56^bright NK cells in these patients.

Conclusion: Our results demonstrated phenotypically suppressed-NK cells, especially in the CD56^bright subset of BC patients. It specifies their potential incompetence and outlines decrement of their anti-tumor activity, which could be interrelated with the tumor pathogenesis, TME immunosuppression, and so disease progression. The induction of compensatory mechanisms revives NK cells function and could be used in combination with the conventional treatments as a putative therapeutic approach for targeted immunotherapy.