The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment.

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.

Hybrid effects of zirconia nanoparticles with aluminum borate whiskers on mechanical properties of denture base resin PMMA.

The aim of this study was to investigate the hybrid effects of ZrO2 nanoparticles (nano-ZrO2) and aluminum borate whiskers (ABWs) on flexural strength and surface hardness of denture base resin, polymethyl methacrylate (PMMA). Both nano-ZrO2 and ABWs were modified by silane coupling agent (Z6030) before being mixed with PMMA. Various amounts of silanized nano-ZrO2 and ABWs were mixed with PMMA to prepare ZrO2-ABW/PMMA composites. Flexural strength and surface hardness were evaluated using three- point bending test and Vickers hardness test respectively. Fractured surfaces were also observed by scanning electron microscopy (SEM). The mechanical behaviors of silanized ZrO2-ABW/PMMA composites were significantly improved. Flexural strength reached a maximum value of 108.01 ± 5.54 MPa when 2 wt% of nano-ZrO2 was mixed with ABWs at a ZrO2/ABW ratio of 1:2, amounting to an increase of 52% when compared with pure PMMA. Surface hardness achieved a maximum value of 22.50 ± 0.86 MPa when 3 wt% of nano-ZrO2 was mixed with ABWs at the same ZrO2/ABW ratio, which was an increase of 27% when compared with pure PMMA.