Suppression of CD56bright NK cells in breast cancer patients is associated with the PD-1 and TGF-BRII 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 CD56dim and CD56bright 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 CD56dim and CD56bright NK subtypes showed lower CXCR3 and NKG2D expression in BC patients than healthy subjects. Furthermore, patients’ CD56bright 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 CD56bright NK cells in these patients. Conclusion Our results demonstrated phenotypically suppressed-NK cells, especially in the CD56bright 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 (AU)

Suppression of CD56bright NK cells in breast cancer patients is associated with the PD-1 and TGF-ßRII 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-ßRII were studied on CD56dim and CD56bright 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 CD56dim and CD56bright NK subtypes showed lower CXCR3 and NKG2D expression in BC patients than healthy subjects. Furthermore, patients' CD56bright NK cells significantly showed higher expression levels of TGF-ßRII and PD-1. Interestingly, increased concentration of MIC-A level in plasma of BC patients was associated with the higher TGF-ßRII and PD-1 expression in all NK cells, while the plasma level of IFN-γ was associated with the lower TGF-ßRII expression on CD56bright NK cells in these patients. CONCLUSION: Our results demonstrated phenotypically suppressed-NK cells, especially in the CD56bright 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.

Natural Killer Cell Defects in Breast Cancer: A Key Pathway for Tumor Evasion.

As the most important innate immune component cancers invader, natural killer (NK) cells have a magnificent role in antitumor immunity without any prior sensitization. Different subsets of NK cells have distinct responses during tumor cell exposure, according to their phenotypes and environments. Their function is induced mainly by the activity of both inhibitory and activating receptors against cancerous cells. Since the immunosuppression in the tumor microenvironment of breast cancer patients has directly deteriorated the phenotype and disturbed the function of NK cells, recruiting compensatory mechanisms indicate promising outcomes for immunotherapeutic approaches. These evidences accentuate the importance of NK cell distinct features in protection against breast tumors. In this review, we discuss the several mechanisms involved in NK cells suppression which consequently promote tumor progression and disease recurrence in patients with breast cancer.