Jing Hao

Seven flavonoid glycosides, including one new (1) and five previously uncharacterized (3-7), were obtained from the seeds of lychee ( Litchi chinensis Sonn. cv. Heiye) by means of repetitive column chromatography and high-performance liquid chromatography (HPLC) preparation. They were identified as litchioside D (1), (-)-pinocembrin 7-O-neohesperidoside (2), (-)-pinocembrin 7-O-rutinoside (3), taxifolin 4'-O-β-d-glucopyranoside (4), kaempferol 7-O-neohesperidoside (5), tamarixetin 3-O-rutinoside (6), and phlorizin (7) on the basis of spectroscopic analysis and comparison of their data to the values reported in the literatures. Among them, compounds 1, 4, and 5 showed in vitro antitumor activity against A549, LAC, Hep-G2, and HeLa cell lines in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay.

Overcoming CD8 + T cell exhaustion is critical in cancer immunotherapy. Recently, an intratumor stem/progenitor-like CD8 + T cell (T prog cell) population that mediates the persistence of antitumor responses has been defined, which can further develop into a terminally differentiated CD8 + T cell (T term cell) subpopulation with potent cytotoxic functions. T prog cells are the main responders to immune checkpoint blockade therapies, yet how extrinsic signals via transcription factors control T prog cell generation and persistence in tumors is unclear. Here, we found that BCL6 inhibits tumor-specific T term cell generation from T prog cell downstream of TCF1. We show that Bcl6 deficiency reduced the persistence of T prog cells, without affecting their generation, thus abrogating long-term tumor control. High-level BCL6 expression was observed in tumor-specific T cells in draining lymph nodes (LNs) and was associated with T cell exhaustion. This was observed in TOX + TCF1 + T prog cells in both LNs and tumors. BCL6 expression in CD8 + T cells was up-regulated by TGF-β–SMAD2 signaling but down-regulated by the IL-2–STAT5 pathway. Mechanistically, BCL6 transcriptionally repressed the expression of T term cell–associated genes and induced those of T prog cell–related genes, in a manner antagonistic to BLIMP1. Prdm1 deficiency also promoted the T prog cell program and greatly improved the efficacy of anti–PD-1 therapy. Thus, we identified the TGF-β–BCL6 and IL-2–BLIMP1 antagonistic pathways in regulation of antitumor CD8 + T cells, which may benefit the development of long-lasting and effective cancer immunotherapy.

BACKGROUND: Nasal polyp (NP) is the most common mass lesion in the nose with unclear etiology and pathogenesis. OBJECTIVE: To investigate the association of allergy and type of cellular inflammation in Asian patients with NPs. METHODS: Immunohistochemical staining with a panel of antibodies for CD4+ and CD8+ T cells, B cells, Langerhans' cells, eosinophils, neutrophils, and mast cells were performed in pairs of NP tissue and middle turbinate (MT) biopsies from the same side of 48 patients and MT of controls. Serum total IgE and specific IgE to a panel of common local allergens were tested by the UniCAP (Pharmacia & Upjohn AB, Uppsala, Sweden) system. RESULTS: Atopy was found in 29.7% of NP patients. Strong correlations of cell scores were evidenced between the paired samples from nasal polyp patients. The cell patterns in nasal polyp mainly showed a combined cell infiltration with significantly higher CD8+ T cell, eosinophil and neutrophil scores, and an inverse median ratio of CD4+/CD8+ T cells as compared with the MT from controls. CONCLUSION: The similar immunohistochemical pattern of mucosal inflammation in NPs and the paired MT mucosa suggests a diffuse mucosal involvement. This indicates the necessity of anti-inflammatory treatment of changes in the adjacent nasal mucosa in addition to the surgical removal of NPs. Besides the well-recognized eosinophilic inflammation in Caucasian studies, predominant infiltration of T cells, especially CD8+ T cells, could be a key component underlying the pathogeneses of NPs.

Gelsolin (GSN) is one of the most abundant actin-binding proteins, and is involved in several pathological processes, including Alzheimer's disease, cardiac injury and cancer. The aim of the present study was to assess the effect of GSN on the growth and motility of oral squamous cell carcinoma Tca8113 cells. The overexpression vector pcDNA3.1-GSN was transfected into Tca8113 cells and the stable GSN overexpression cell line was identified based on G418 antibiotic selection. The effect of GSN overexpression on the proliferation, apoptosis, migration and invasion of Tca8113 cells was examined using a cell counting kit-8 assay, flow cytometry and Transwell assays. The results revealed that GSN overexpression significantly promoted the cell proliferation and apoptosis of Tca8113 cells. In addition, Transwell assays demonstrated that the migration and invasion abilities of Tca8113 cells were enhanced by GSN overexpression. Therefore, the upregulation of GSN promotes cell growth and motility, indicating that it may perform a vital function in the progression of human oral cancers.