Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1.

PD-1 is a co-inhibitory receptor expressed by CD8+ T cells which limits their cytotoxicity. PD-L1 expression on cancer cells contributes to immune evasion by cancers, thus, understanding the mechanisms that regulate PD-L1 protein levels in cancers is important. Here we identify tumor-cell-expressed otubain-2 (OTUB2) as a negative regulator of antitumor immunity, acting through the PD-1/PD-L1 axis in various human cancers. Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum. Genetic deletion of OTUB2 markedly decreases the expression of PD-L1 proteins on the tumor cell surface, resulting in increased tumor cell sensitivity to CD8+ T-cell-mediated cytotoxicity. To underscore relevance in human patients, we observe a significant correlation between OTUB2 expression and PD-L1 abundance in human non-small cell lung cancer. An inhibitor of OTUB2, interfering with its deubiquitinase activity without disrupting the OTUB2-PD-L1 interaction, successfully reduces PD-L1 expression in tumor cells and suppressed tumor growth. Together, these results reveal the roles of OTUB2 in PD-L1 regulation and tumor evasion and lays down the proof of principle for OTUB2 targeting as therapeutic strategy for cancer treatment.

Transient dynamics of the phase transition in VO2 revealed by mega-electron-volt ultrafast electron diffraction.

Vanadium dioxide (VO2) exhibits an insulator-to-metal transition accompanied by a structural transition near room temperature. This transition can be triggered by an ultrafast laser pulse. Exotic transient states, such as a metallic state without structural transition, were also proposed. These unique characteristics let VO2 have great potential in thermal switchable devices and photonic applications. Although great efforts have been made, the atomic pathway during the photoinduced phase transition is still not clear. Here, we synthesize freestanding quasi-single-crystal VO2 films and examine their photoinduced structural phase transition with mega-electron-volt ultrafast electron diffraction. Leveraging the high signal-to-noise ratio and high temporal resolution, we observe that the disappearance of vanadium dimers and zigzag chains does not coincide with the transformation of crystal symmetry. After photoexcitation, the initial structure is strongly modified within 200 femtoseconds, resulting in a transient monoclinic structure without vanadium dimers and zigzag chains. Then, it continues to evolve to the final tetragonal structure in approximately 5 picoseconds. In addition, only one laser fluence threshold instead of two thresholds suggested in polycrystalline samples is observed in our quasi-single-crystal samples. Our findings provide essential information for a comprehensive understanding of the photoinduced ultrafast phase transition in VO2.

Coexistence of Ferroelectriclike Polarization and Dirac-like Surface State in TaNiTe_{5}.

By combining angle-resolved photoemission spectroscopy, scanning tunneling microscopy, atomic force microscope based piezoresponse force microscopy and first-principles calculations, we have studied the low-energy band structure, atomic structure, and charge polarization on the surface of a topological semimetal candidate TaNiTe_{5}. Dirac-like surface states were observed on the (010) surface by angle-resolved photoemission spectroscopy, consistent with the first-principles calculations. On the other hand, piezoresponse force microscopy reveals a switchable ferroelectriclike polarization on the same surface. We propose that the noncentrosymmetric surface relaxation observed by scanning tunneling microscopy could be the origin of the observed ferroelectriclike state in this novel material. Our findings provide a new platform with the coexistence of a ferroelectriclike surface charge distribution and novel surface states.