RESUMEN
Natural killer (NK) cells, as innate lymphocytes, possess cytotoxic capabilities and engage target cells through a repertoire of activating and inhibitory receptors. Particularly, natural killer group 2, member D (NKG2D) receptor on NK cells recognizes stress-induced ligands-the MHC class I chain-related molecules A and B (MICA/B) presented on tumor cells and is key to trigger the cytolytic response of NK cells. However, tumors have developed sophisticated strategies to evade NK cell surveillance, which lead to failure of tumor immunotherapy. In this paper, we summarized these immune escaping strategies, including the downregulation of ligands for activating receptors, upregulation of ligands for inhibitory receptors, secretion of immunosuppressive compounds, and the development of apoptosis resistance. Then, we focus on recent advancements in NK cell immune therapies, which include engaging activating NK cell receptors, upregulating NKG2D ligand MICA/B expression, blocking inhibitory NK cell receptors, adoptive NK cell therapy, chimeric antigen receptor (CAR)-engineered NK cells (CAR-NK), and NKG2D CAR-T cells, especially several vaccines targeting MICA/B. This review will inspire the research in NK cell biology in tumor and provide significant hope for improving cancer treatment outcomes by harnessing the potent cytotoxic activity of NK cells.
RESUMEN
Conducting polymer hydrogels, especially poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels, show great promise in soft bioelectronics due to their high conductivity and the ability of electrical coupling with tissues for sensing and stimulation. However, it is challenging to solve the problem of poor biocompatibility of PEDOT:PSS hydrogels due to the existing harsh preparation methods with the use of toxic and harmful reagents. Herein, we report the synthesis of PEDOT:PSS hydrogels with positively charged conductive polymers as a cross-linker and the application of PEDOT:PSS hydrogels as in situ electrochemical sensors for living cells. The conductivities of PEDOT:PSS hydrogels prepared using this method without any toxic or harmful reagents can reach up to 3265 S m-1. The facile synthesis approach with a simple mixture of PEDOT:PSS aqueous solution and the monomers of conductive polymers at room temperature also enables the printability of PEDOT:PSS hydrogels to fabricate patterned electrodes. Moreover, all the proposed PEDOT:PSS hydrogels demonstrated good biocompatibility. The in situ electrochemical detection of dopamine secreted from PC12 cells cultured within PEDOT:PSS hydrogels suggests that our PEDOT:PSS hydrogels with high conductivity and biocompatibility offer great potential for the integration of biosensors within 3D cell culture.
