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MXenes belong to a large family of two-dimensional layered transition-metal carbides and nitrides. MXene nanosheets integrate the fascinating advantages of high electronic conductivity, excellent biocompatibility, and acid/base resistance. Herein, we demonstrate a “hospital-on-a-chip” system with multifunctional microneedle electrodes for biosensing and electrostimulation using highly stable MXene nanosheets. This system consists of integrated microchip biosensors for an efficient diagnosis and medical treatment elements for therapies, thus resembling a miniaturized hospital. Microneedles are composed of dozens of micron-sized needles that can be used as an effective and painless transdermal patch to puncture the dead skin barrier for drug delivery or biosensing purposes since they are directly in contact with the dermal layer inside the human body. The wearable MXene nanosheet-based microneedles can sense the tiny electric potential difference generated from the human eye movements or muscle contraction from the human arm. Therefore, the diseases associated with neuromuscular abnormalities such as myasthenia gravis can be monitored. Consequently, the transcutaneous electrical nerve stimulation treatment can be applied according to the feedback of the micro-biosensors. In addition, MXene microneedles can offer an electrically controlled drug delivery platform and the function of enhancing blood coagulation. Finally, MXene nanosheet-based microneedles provide an interesting platform for wearable micro-biosensors and offer an essential part of the hospital-on-a-chip system.

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CD28 is required for T cell activation as well as the generation of CD4+Foxp3+ Treg. It is unclear, however, how CD28 costimulation affects the development of CD8+ T cell suppressive function. Here, by use of Hepa1.6.gp33 in vitro killing assay and B16.gp33 tumor mouse model we demonstrate that CD28 engagement during TCR ligation prevents CD8+ T cells from becoming suppressive. Interestingly, our results showed that ectonucleotidase CD73 expression on CD8+ T cells is upregulated in the absence of CD28 costimulation. In both murine and human tumor-bearing hosts, CD73 is upregulated on CD28−CD8+ T cells that infiltrate the solid tumor. UPLC-MS/MS analysis revealed that CD8+ T cells activation without CD28 costimulation produces elevated levels of adenosine and that CD73 mediates its production. Adenosine receptor antagonists block CD73-mediated suppression. Our data support the notion that CD28 costimulation inhibits CD73 upregulation and thereby prevents CD8+ T cells from becoming suppressive. This study uncovers a previously unidentified role for CD28 costimulation in CD8+ T cell activation and suggests that the CD28 costimulatory pathway can be a potential target for cancer immunotherapy.