S100A9 and HMGB1 orchestrate MDSC-mediated immunosuppression in melanoma through TLR4 signaling.

Background: Immunotherapies for malignant melanoma are challenged by the resistance developed in a significant proportion of patients. Myeloid-derived suppressor cells (MDSC), with their ability to inhibit antitumor T-cell responses, are a major contributor to immunosuppression and resistance to immune checkpoint therapies in melanoma. Damage-associated molecular patterns S100A8, S100A9, and HMGB1, acting as toll like receptor 4 (TLR4) and receptor for advanced glycation endproducts (RAGE) ligands, are highly expressed in the tumor microenvironment and drive MDSC activation.

Giant hyperfine interaction between a dark exciton condensate and nuclei.

We study the interaction of a dark exciton Bose-Einstein condensate with the nuclei in gallium arsenide/aluminum gallium arsenide coupled quantum wells and find clear evidence for nuclear polarization buildup that accompanies the appearance of the condensate. We show that the nuclei are polarized throughout the mesa area, extending to regions that are far away from the photoexcitation area and persisting for seconds after the excitation is switched off. Photoluminescence measurements in the presence of radio frequency radiation reveal that the hyperfine interaction between the nuclear and electron spins is enhanced by two orders of magnitude.

Sphinganine recruits TLR4 adaptors in macrophages and promotes inflammation in murine models of sepsis and melanoma.

After recognizing its ligand lipopolysaccharide, Toll-like receptor 4 (TLR4) recruits adaptor proteins to the cell membrane, thereby initiating downstream signaling and triggering inflammation. Whether this recruitment of adaptor proteins is dependent solely on protein-protein interactions is unknown. Here, we report that the sphingolipid sphinganine physically interacts with the adaptor proteins MyD88 and TIRAP and promotes MyD88 recruitment in macrophages.

Generation of Myeloid-Derived Suppressor Cells Mediated by MicroRNA-125a-5p in Melanoma.

The ability of tumor-derived extracellular vesicles (EVs) to modulate the function of myeloid cells is widely recognized. Hence, a comprehensive understanding of the distinct components associated with EVs and the signals that they deliver to myeloid cells could provide potential approaches to impede the immunosuppression by myeloid-derived suppressor cells (MDSCs). We investigated melanoma EV-associated microRNAs (miRs) using the RET transgenic melanoma mouse model and simulated their transfer to normal myeloid cells by transfecting immature mouse myeloid cells and human monocytes.

Myeloid-derived suppressor cells in peripheral blood as predictive biomarkers in patients with solid tumors undergoing immune checkpoint therapy: systematic review and meta-analysis.

Background: Immunotherapeutic approaches, including immune checkpoint inhibitor (ICI) therapy, are increasingly recognized for their potential. Despite notable successes, patient responses to these treatments vary significantly. The absence of reliable predictive and prognostic biomarkers hampers the ability to foresee outcomes.

Measuring statistics-induced entanglement entropy with a Hong-Ou-Mandel interferometer.

Despite its ubiquity in quantum computation and quantum information, a universally applicable definition of quantum entanglement remains elusive. The challenge is further accentuated when entanglement is associated with other key themes, e.g.

Anomalous Aharonov-Bohm Interference in the Presence of Edge Reconstruction.

Interferometry is a vital tool for studying fundamental features in the quantum Hall effect. For instance, Aharonov-Bohm interference in a quantum Hall interferometer can probe the wave-particle duality of electrons and quasiparticles. Here, we report an unusual Aharonov-Bohm interference of the outermost edge mode in a quantum Hall Fabry-Pérot interferometer, whose Coulomb interactions were suppressed with a grounded drain in the interior bulk of the interferometer.

Myeloid-derived suppressor cells in cancer and cancer therapy.

Anticancer agents continue to dominate the list of newly approved drugs, approximately half of which are immunotherapies. This trend illustrates the considerable promise of cancer treatments that modulate the immune system. However, the immune system is complex and dynamic, and can have both tumour-suppressive and tumour-promoting effects.

Heat conductance of the quantum Hall bulk.

The quantum Hall effect is a prototypical realization of a topological state of matter. It emerges from a subtle interplay between topology, interactions and disorder. The disorder enables the formation of localized states in the bulk that stabilize the quantum Hall states with respect to the magnetic field and carrier density.

Electron Pairing of Interfering Interface-Based Edge Modes.

The remarkable Cooper-like pairing phenomenon in the Aharonov-Bohm interference of a Fabry-Perot interferometer-operating in the integer quantum Hall regime-remains baffling. Here, we report the interference of paired electrons employing "interface edge modes." These modes are born at the interface between the bulk of the Fabry-Perot interferometer and an outer gated region tuned to a lower filling factor.

Melanoma patients with immune-related adverse events after immune checkpoint inhibitors are characterized by a distinct immunological phenotype of circulating T cells and M-MDSCs.

Treatment with immune checkpoint inhibitors (ICIs) has improved the prognosis of melanoma patients. However, ICIs can cause an overactivation of the immune system followed by diverse immunological side effects known as immune-related adverse events (irAE). Currently, the toxicity of irAE is limiting the usage of ICIs.

Enhancing immunotherapy response in melanoma: myeloid-derived suppressor cells as a therapeutic target.

Despite the remarkable success of immune checkpoint inhibitors (ICIs) in melanoma treatment, resistance to them remains a substantial clinical challenge. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid cells that can suppress antitumor immune responses mediated by T and natural killer cells and promote tumor growth. They are major contributors to ICI resistance and play a crucial role in creating an immunosuppressive tumor microenvironment.

Wigner-molecularization-enabled dynamic nuclear polarization.

Multielectron semiconductor quantum dots (QDs) provide a novel platform to study the Coulomb interaction-driven, spatially localized electron states of Wigner molecules (WMs). Although Wigner-molecularization has been confirmed by real-space imaging and coherent spectroscopy, the open system dynamics of the strongly correlated states with the environment are not yet well understood. Here, we demonstrate efficient control of spin transfer between an artificial three-electron WM and the nuclear environment in a GaAs double QD.

Secretogranin II influences the assembly and function of MHC class I in melanoma.

Melanoma is the deadliest form of skin cancer showing rising incidence over the past years. New insights into the mechanisms of melanoma progression contributed to the development of novel treatment options, such as immunotherapies. However, acquiring resistance to treatment poses a big problem to therapy success.

Immunosuppressive capacity of circulating MDSC predicts response to immune checkpoint inhibitors in melanoma patients.

Purpose: Although the treatment of advanced melanoma patients with immune checkpoint inhibitors (ICI) significantly increased the therapeutic efficiency, many patients remain resistant to ICI that could be due to immunosuppression mediated by myeloid-derived suppressor cells (MDSC). These cells are enriched and activated in melanoma patients and could be considered as therapeutic targets. Here we studied dynamic changes in immunosuppressive pattern and activity of circulating MDSC from melanoma patients treated with ICI.

Observation of electronic modes in open cavity resonator.

The resemblance between electrons and optical waves has strongly driven the advancement of mesoscopic physics, evidenced by the widespread use of terms such as fermion or electron optics. However, electron waves have yet to be understood in open cavity structures which have provided contemporary optics with rich insight towards non-Hermitian systems and complex interactions between resonance modes. Here, we report the realization of an open cavity resonator in a two-dimensional electronic system.

Booster dose of mRNA vaccine augments waning T cell and antibody responses against SARS-CoV-2.

A gradual decay in humoral and cellular immune responses over time upon SAR1S-CoV-2 vaccination may cause a lack of protective immunity. We conducted a longitudinal analysis of antibodies, T cells, and monocytes in 25 participants vaccinated with mRNA or ChAdOx1-S up to 12 weeks after the 3 (booster) dose with mRNA vaccine. We observed a substantial increase in antibodies and CD8 T cells specific for the spike protein of SARS-CoV-2 after vaccination.

HSP90α induces immunosuppressive myeloid cells in melanoma via TLR4 signaling.

Background: Tumor cells modulate host immunity by secreting extracellular vesicles (EV) and soluble factors. Their interactions with myeloid cells lead to the generation of myeloid-derived suppressor cells (MDSC), which inhibit the antitumor function of T and NK cells. We demonstrated previously that EV derived from mouse and human melanoma cells induced immunosuppressive activity via increased expression of programmed cell death ligand 1 (PD-L1) on myeloid cells that was dependent on the heat-shock protein 90α (HSP90α) in EV.

Isolated ballistic non-abelian interface channel.

The topological order of a quantum Hall state is mirrored by the gapless edge modes owing to bulk-edge correspondence. The state at the filling of ν = 5/2, predicted to host non-abelian anyons, supports a variety of edge modes (integer, fractional, neutral). To ensure thermal equilibration between the edge modes and thus accurately determine the state's nature, it is advantageous to isolate the fractional channel (1/2 and neutral modes).

Approaching Ideal Visibility in Singlet-Triplet Qubit Operations Using Energy-Selective Tunneling-Based Hamiltonian Estimation.

We report energy-selective tunneling readout-based Hamiltonian parameter estimation of a two-electron spin qubit in a GaAs quantum dot array. Optimization of readout fidelity enables a single-shot measurement time of 16  μs on average, with adaptive initialization and efficient qubit frequency estimation based on real-time Bayesian inference. For qubit operation in a frequency heralded mode, we observe a 40-fold increase in coherence time without resorting to dynamic nuclear polarization.

The Role of Spin-Flip Collisions in a Dark-Exciton Condensate.

We show that a Bose-Einstein condensate consisting of dark excitons forms in GaAs coupled quantum wells at low temperatures. We find that the condensate extends over hundreds of micrometers, well beyond the optical excitation region, and is limited only by the boundaries of the mesa. We show that the condensate density is determined by spin-flipping collisions among the excitons, which convert dark excitons into bright ones.

Cross-talk between HIF and PD-1/PD-L1 pathways in carcinogenesis and therapy.

Tumor-associated hypoxia plays an important role in carcinogenesis and metastasis. The expression, activation, and stabilization of hypoxia-inducible transcription factors (HIFs) support malignant cell survival, proliferation, plasticity, and motility. Hypoxia also upregulates the expression of programmed cell death ligand 1 (PD-L1) in malignant and immune regulatory cells.

STAT3 inhibitor Napabucasin abrogates MDSC immunosuppressive capacity and prolongs survival of melanoma-bearing mice.

Background: Myeloid-derived suppressor cells (MDSCs) represent a negative prognostic factor in malignant melanoma. These cells are generated under chronic inflammatory conditions typical of cancer. The transcription factor signal transducer and activator of transcription 3 (STAT3) orchestrates MDSC accumulation and acquisition of immunosuppressive properties.