Objective To study the effect of neurotrophic tyrosine kinase receptor B(TrKB) on in vitro invasiveness of malignant transformed hFOB1.19 cells and the role of TrKB in invasion and metastasis of osteosarcoma.Methods Expression of TrKB in malignant transformed hFOB1.19 cells and SaOS-2 osteosarcoma cells was detected by RT-PCR and immunofluorescence.Function of TrKB of malignant transformed hFOB1.19 cells was further studied.Malignant transformed hFOB1.19 cells were treated with specific tyrosine kinase inhibitor K252a for 24 h as a treatment group,and untreated malignant transformed hFOB1.19 cells into which DMSO was added served as a control group.Morphology of cells was observed under an inverted phase contrast microscope.Cell invasiveness was detected by Transwell assays.Microfilaments of cells were detected by actin immunofluorescence.Results The expression of TrKB was significantly higher in malignant transformed hFOB1.19 cells than in SaOS-2 osteosarcoma cells(P

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8⁺PD1⁺TCF1⁺ progenitor exhausted T cells (TCF1⁺Tex^prog) and CD8⁺PD1⁺TCF1^- terminally exhausted T cells (TCF1^-Tex^term). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1^-Tex^term represented a greater proportion of CD8⁺PD1⁺Tex than TCF1⁺Tex^prog in most patients. TCF1⁺Tex^prog produced abundant TNFα, while TCF1^-Tex^term expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1^-Tex^term exhibited a polyfunctional TNFα⁺GZMB⁺IFNγ⁺ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1^-Tex^term were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1^-Tex^term was the major CD8⁺PD1⁺Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1^-Tex^term was associated with greater Treg abundance.
CD8-Positive T-Lymphocytes ; Head and Neck Neoplasms/therapy* ; Humans ; Immunotherapy/methods* ; Prognosis ; Programmed Cell Death 1 Receptor ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha