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BACKGROUND. The PD-1–blocking antibody nivolumab persists in patients several weeks after the last infusion. However, no study has systematically evaluated the maximum duration that the antibody persists on T cells or the association between this duration and residual therapeutic efficacy or potential adverse events.METHODS. To define the duration of binding and residual efficacy of nivolumab after discontinuation, we developed a simplified strategy for T cell monitoring and used it to analyze T cells from peripheral blood from 11 non–small cell lung cancer patients previously treated with nivolumab. To determine the suitability of our method for other applications, we compared transcriptome profiles between nivolumab-bound and nivolumab-unbound CD8 T cells. We also applied T cell monitoring in 2 nivolumab-treated patients who developed progressive lung tumors during long-term follow-up.RESULTS. Prolonged nivolumab binding was detected more than 20 weeks after the last infusion, regardless of the total number of nivolumab infusions (2–15 doses) or type of subsequent treatment, in 9 of the 11 cases in which long-term monitoring was possible. Ki-67 positivity, a proliferation marker, in T cells decreased in patients with progressive disease. Transcriptome profiling identified the signals regulating activation of nivolumab-bound T cells, which may contribute to nivolumab resistance. In 2 patients who restarted nivolumab, T cell proliferation markers exhibited the opposite trend and correlated with clinical response.CONCLUSIONS. Although only a few samples were analyzed, our strategy of monitoring both nivolumab binding and Ki-67 in T cells might help determine residual efficacy under various types of concurrent or subsequent treatment.TRIAL REGISTRATION. University Hospital Medical Information Network Clinical Trials Registry, UMIN000024623.FUNDING. This work was supported by Japan Society for the Promotion of Science KAKENHI (JP17K16045, JP18H05282, and JP15K09220), Japan Agency for Medical Research and Development (JP17cm0106310, JP18cm0106335 and JP18cm059042), and Core Research for Evolutional Science and Technology (JPMJCR16G2).

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Polarized light emission was observed in conjugated polymer electroluminescent diodes comprising rubbing-aligned poly(2,5-dinonyloxy-1,4-phenylenevinylene) as the emissive layer. By using 2-(4-biphenyly1)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole dispersed in polystyrene as the electron-transporting/hole-blocking layer, the electroluminescence efficiency and the dichroic ratio of the electroluminescent light increased, resulting in polarized electroluminescence with a dichroic ratio of 4.0.

Oligodendrocyte maturation is necessary for functional regeneration in the CNS; however, the mechanisms by which the systemic environment regulates oligodendrocyte maturation is unclear. We found that Transforming growth factor (TGF)-β1, which is present in higher levels in the systemic environment, promotes oligodendrocyte maturation. Oligodendrocyte maturation was enhanced by adult mouse serum treatment via TGF-β type I receptor. Decrease in circulating TGF-β1 level prevented remyelination in the spinal cord after toxin-induced demyelination. TGF-β1 administration promoted remyelination and restored neurological function in a multiple sclerosis animal model. Furthermore, TGF-β1 treatment stimulated human oligodendrocyte maturation. These data provide the therapeutic possibility of TGF-β for demyelinating diseases.

A preferred molecular orientation in a conjugated polymer, poly(2,5-dinonyloxy-1,4-phenylenevinylene) (NO-PPV), can be obtained by a unidirectional rubbing treatment of its thin solid film. Polarized electroluminescence with dichroic ratio of 1.6 as well as anisotropic optical absorption and photoluminescence have been observed for the rubbed NO-PPV film. An analysis of orientation distribution in the rubbed NO-PPV film suggested that radiative decay occurs in both oriented and unoriented layers. Surface geometry measurements suggested that plastic deformation of the polymer along the rubbing direction was the cause of the preferred orientation even in the conjugated polymer with rigid main chain structure.

We show that polarity-dependent, nonvolatile resistance switching by electric field occurs in the thin film of various transition-metal oxides in almost the same manner. This result indicates that, contrary to the general acceptance, perovskite manganite is by no means a special compound for this phenomenon. It is also suggested that the resistance switching is not dominated by a detailed electronic structure of each sample, but dominated by a more general origin, e.g., crystalline defect.

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