The effects of trastuzumab on the CD4+CD25+FoxP3+ and CD4+IL17A+ T-cell axis in patients with breast cancer

In addition to the direct targeting effects on HER2-positive cells, trastuzumab may have a therapeutic role modulating the activity of the cellular immune system in patients with breast cancer. To investigate this further, the balance of T-regulatory (Treg), Th17, natural killer (NK) and NK T (NKT) cells before, during and after trastuzumab therapy was investigated. Sequential frequencies of circulating Treg cells, Th17 cells, NK and NKT cells were measured in peripheral blood of breast cancer patients and normal controls throughout therapy. Individuals with breast cancer had significantly higher Treg frequencies of peripheral blood compared with healthy controls (9.2 or 8.6 vs 6%; P<0.05), and no significant differences in Treg frequencies were observed between HER2-positive and HER2-negative individuals. The number of Th17 cells was lowest in HER2-positive patients compared with both healthy controls and HER2-negative patients (0.31 vs 0.75% or 0.84%; P=0.01). There appeared to be an inverse relationship between Treg and Th17 frequencies in metastatic breast cancer (MBC) with Treg levels significantly reduced during treatment with trastuzumab (P=0.04), whereas Th17 frequencies were concomitantly increased (P=0.04). This study supports earlier data that Treg cells are present at higher frequencies in breast cancer patients compared with healthy individuals. For the first time, we show that HER2-positive individuals with breast carcinomas have reduced numbers of circulating Th17 cells, which appear, in turn to have an inverse relationship with Treg frequency in MBC. The change in balance of the Treg : Th17 ratio appears to characterise the cancer state, and furthermore, is disrupted by trastuzumab therapy

Introducing a 3-dimensionally Printed, Tissue-Engineered Graft for Airway Reconstruction: A Pilot Study

OBJECTIVE: To use 3-dimensional (3D) printing and tissue engineering to create a graft for laryngotracheal reconstruction (LTR). STUDY DESIGN: In vitro and in vivo pilot animal study. SETTING: Large tertiary care academic medical center. SUBJECTS AND METHODS: A 3D computer model of an anterior LTR graft was designed. That design was printed with polylactic acid on a commercially available 3D printer. The scaffolds were seeded with mature chondrocytes and collagen gel and cultured in vitro for up to 3 weeks. Scaffolds were evaluated in vitro for cell viability and proliferation. Anterior graft LTR was performed on 9 New Zealand white rabbits with the newly created scaffolds. Three animals were sacrificed at each time point (4, 8, and 12 weeks). The in vivo graft sites were assessed via bronchoscopy and histology. RESULTS: The in vitro cell proliferation assay demonstrated initial viability of 87.5%. The cells proliferated during the study period, doubling over the first 7 days. Histology revealed that the cells retained their cartilaginous properties during the 21-day study period. In vivo testing showed that all animals survived for the duration of the study. Bronchoscopy revealed a well-mucosalized tracheal lumen with no evidence of scarring or granulation tissue. Histology indicated the presence of newly formed cartilage in the region where the graft was present. CONCLUSIONS: Our results indicate that it is possible to produce a custom-designed, 3D-printed, tissue-engineered graft for airway reconstruction