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.

Biosimilarity Assessment of 2 Filgrastim Therapeutics in Healthy Volunteers.

This study aimed to compare the pharmacokinetic, pharmacodynamic, and safety profiles of a proposed biosimilar and innovator filgrastim therapeutics in healthy volunteers. In a crossover design, 23 subjects received a single subcutaneous injection of 300-µg filgrastim, followed by a 7-day washout period. Assessed pharmacokinetic parameters were the maximum observed filgrastim serum concentration (Cmax ), time to reach Cmax (tmax ), the area under the concentration-time curve (AUC), and elimination half-life. Pharmacodynamics were assessed by the maximum observed absolute neutrophil count effect (Emax ), tmax,E (time to reach Emax ), and the area under the effect of the absolute neutrophil count -time curve. The test/reference ratio (90% confidence intervals) of Cmax of 0.992 (0.860-1.143), AUC0-inf of 0.995 (0.891-1.111), Emax of 0.952 (0.841, 1.078), and area under the effect of the absolute neutrophil count -time curve from time zero to 96 hours of 0.939 (0.854-1.032), were all well within the predefined equivalence boundaries of 80% and 125%. Obtained values for tmax (∼4 hours), tmax,E (∼15 hours), and elimination half-life (∼3.5 hours) were comparable between 2 treatment groups. The local tolerability and incidence of adverse events were comparable, with no clinically meaningful difference between biosimilar and innovator products. Altogether, the results suggested a high similarity of the proposed biosimilar to the innovator filgrastim in healthy volunteers.

Neglected foreign body aspiration mimicking bronchial carcinoma.

Foreign body aspiration can occur in any age group, but it is more commonly seen in children. In adults, there is usually a predisposing condition that poses a risk of aspiration. If aspiration occurs, prompt diagnosis and extraction of the foreign body is needed to prevent early and late complications. We report a rare case of neglected foreign body aspiration in a 45-year-old schizophrenic opium addicted patient, which resulted in an occlusive lesion in the bronchus, mimicking bronchial carcinoma.