RESUMEN
B and T lymphocyte attenuator (BTLA) is an immune checkpoint molecule that mediates the escape of tumor cells from immunosurveillance. Consequently, BTLA and its ligand herpesvirus entry mediator (HVEM) are potentially immunotherapeutic targets. However, the potential effects of BTLA on tumor cells remain incompletely unknown. Here, we show that BTLA is expressed across a broad range of tumor cells. The depletion of BTLA or HVEM promotes cell proliferation and colony formation, which is reversed by the overexpression of BTLA in BTLA knockout cells. In contrast, overexpression of BTLA or HVEM inhibits tumor cell proliferation and colony formation. Furthermore, the proliferation of a subpopulation with high BTLA was also significantly slower than that of the low BTLA subpopulation. Mechanistically, the coordination of BTLA and HVEM inhibits its major downstream extracellular regulated protein kinase (ERK1/2) signaling pathway, thus preventing tumor cell growth. This study demonstrates that tumor cell-intrinsic BTLA/HVEM is a potential tumor suppressor and is likely to have a potential antagonist for immunotherapy, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment.
Asunto(s)
Neoplasias , Receptores Inmunológicos , Humanos , Proliferación Celular , Sistema de Señalización de MAP Quinasas , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores Inmunológicos/metabolismo , Subgrupos de Linfocitos T/metabolismoRESUMEN
When changing surface wettability and nanostructure size, condensation behavior displays distinct features. In this work, we investigated evaporation on a flat hydrophilic surface and condensation on both hydrophilic and hydrophobic nanostructured surfaces at the nanoscale using molecular dynamics simulations. The simulation results on hydrophilic surfaces indicated that larger groove widths and heights produced more liquid argon atoms, a quicker temperature response, and slower potential energy decline. These three characteristics closely relate to condensation areas or rates, which are determined by groove width and height. For condensation heat transfer, when the groove width was small, the change of groove height had little effect, while change of groove height caused a significant variation in the heat flux with a large groove width. When the cold wall was hydrophobic, the groove height became a significant impact factor, which caused no vapor atoms to condense in the groove with a larger height. The potential energy decreased with the increase of the groove height, which demonstrates a completely opposing trend when compared with hydrophilic surfaces.