Infrared Resonance Raman of Bilayer Graphene: Signatures of Massive Fermions and Band Structure on the 2D Peak.

Few-layer graphene possesses low-energy carriers that behave as massive Fermions, exhibiting intriguing properties in both transport and light scattering experiments. Lowering the excitation energy of resonance Raman spectroscopy down to 1.17 eV, we target these massive quasiparticles in the split bands close to the K point. The low excitation energy weakens some of the Raman processes that are resonant in the visible, and induces a clearer frequency-separation of the substructures of the resonance 2D peak in bi- and trilayer samples. We follow the excitation-energy dependence of the intensity of each substructure, and comparing experimental measurements on bilayer graphene with ab initio theoretical calculations, we trace back such modifications on the joint effects of probing the electronic dispersion close to the band splitting and enhancement of electron-phonon matrix elements.

Excitonic Effects in Energy-Loss Spectra of Freestanding Graphene.

In this work, we perform electron energy-loss spectroscopy (EELS) of freestanding graphene with high energy and momentum resolution to disentangle the quasielastic scattering from the excitation gap of Dirac electrons close to the optical limit. We show the importance of many-body effects on electronic excitations at finite transferred momentum by comparing measured EELS to ab initio calculations at increasing levels of theory. Quasi-particle corrections and excitonic effects are addressed within the GW approximation and the Bethe-Salpeter equation, respectively. Both effects are essential in the description of the EEL spectra to obtain a quantitative agreement with experiments, with the position, dispersion, and shape of both the excitation gap and the π plasmon being significantly affected by excitonic effects.

Mechanisms of Resistance to Immunotherapy in Hepatocellular Carcinoma.

Systemic treatment for advanced hepatocellular carcinoma (HCC) has been revolutionized over the last few years following the approval of immune checkpoint inhibitors (ICI). Despite the promising survival extension seen with ICI combination regimens, responses are not universally seen and the optimal partner for programmed cell death 1 pathway inhibitors remains to be identified. Even fewer encouraging results have been demonstrated with ICI used for monotherapy. Several mechanisms of resistance have been described so far, involving characteristics of cancer cells (intrinsic mechanisms) and of the surrounding tumor microenvironment (extrinsic mechanisms). Factors related to therapy may also contribute to the development of resistance. Increasing research efforts are being dedicated to the discovery of novel approaches and targets to overcome resistance, some of which may be introduced into clinic in the future. Herein we describe a selection of resistance mechanisms that have been involved in impairing response to ICI and propose potential therapeutic approaches to overcome resistance.

Probing Enhanced Electron-Phonon Coupling in Graphene by Infrared Resonance Raman Spectroscopy.

We report on resonance Raman spectroscopy measurements with excitation photon energy down to 1.16 eV on graphene, to study how low-energy carriers interact with lattice vibrations. Thanks to the excitation energy close to the Dirac point at K, we unveil a giant increase of the intensity ratio between the double-resonant 2D and 2D^{'} peaks with respect to that measured in graphite. Comparing with fully ab initio theoretical calculations, we conclude that the observation is explained by an enhanced, momentum-dependent coupling between electrons and Brillouin zone-boundary optical phonons. This finding applies to two-dimensional Dirac systems and has important consequences for the modeling of transport in graphene devices operating at room temperature.

Integrated phenotyping of the anti-cancer immune response in HIV-associated hepatocellular carcinoma.

Background & Aims: HIV-seropositivity shortens survival in patients with hepatocellular carcinoma (HCC). Although risk factors for HCC including HCV infection can influence T cell phenotype, it is unknown whether HIV can influence functional characteristics of the T cell infiltrate. Methods: From the Liver Cancer in HIV biorepository, we derived 129 samples of transplanted (76%) or resected (20%) HCC in eight European and North American centres. We profiled intra- and peritumoural tissue to evaluate regulatory CD4+/FOXP3+ and immune-exhausted CD8+/PD1+ T cells in HIV+ (n = 66) and HIV- (n = 63) samples. We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples evaluated in relationship with HIV status. We correlated immunopathologic features with patients' characteristics including markers of HIV infection. Results: Of the 66 HIV+ patients, 83% were HCV coinfected with an undetectable HIV viral load (51%) and a median blood CD4+ cell count of 430 cells/mm3 (range 15-908). Patients who were HIV+ were compared with HIV- controls with similar staging characteristics including Barcelona Clinic Liver Cancer (BCLC) stage A-B (86% vs. 83%, p = 0.16), <3 nodules (90% vs. 83%, p = 0.3) and median alpha-foetoprotein values (10.9 vs. 12.8 ng/ml, p = 0.72). HIV+ samples had higher PD-L1 expression rates in tumour tissue (51% vs. 8% p <0.0001) and displayed denser intratumoural CD4+/FOXP3+ (p <0.0001), CD8+/PD1+ (p <0.0001), with lower total peritumoural CD4+ (p <0.0001) and higher peritumoural CD8+/PD1+ (p <0.0001). Gene set analysis revealed HIV+ cases to have evidence of dysregulated adaptive and innate immunity. Tumour-infiltrating lymphocyte clonality was not influenced by HIV status. Conclusions: HIV-associated HCC harbours a profoundly immune-exhausted tumour microenvironment, warranting prospective testing of immunotherapy in this treatment-deprived patient population. Impact and Implications: Hepatocellular carcinoma is a non-AIDS defining malignancy characterised by poor survival. The programmed cell death (PD-1) pathway governs antiviral and anticancer immune exhaustion and is a therapeutic target in HCC. This study highlights how HIV infection is associated with significantly higher PD-L1 expression in HCC cells and in the surrounding microenvironment, leading to changes in cytotoxic and regulatory T cell function and dysregulation of proinflammatory pathways. Taken together, our results suggest dysfunctional T cell immunity as a mechanism of worse outcome in these patients and suggest clinical testing of checkpoint inhibitors in HIV-associated HCC.

Tumor and local lymphoid tissue interaction determines prognosis in high-grade serous ovarian cancer.

Tertiary lymphoid structure (TLS) is associated with prognosis in copy-number-driven tumors, including high-grade serous ovarian cancer (HGSOC), although the function of TLS and its interaction with copy-number alterations in HGSOC are not fully understood. In the current study, we confirm that TLS-high HGSOC patients show significantly better progression-free survival (PFS). We show that the presence of TLS in HGSOC tumors is associated with B cell maturation and cytotoxic tumor-specific T cell activation and proliferation. In addition, the copy-number loss of IL15 and CXCL10 may limit TLS formation in HGSOC; a list of genes that may dysregulate TLS function is also proposed. Last, a radiomics-based signature is developed to predict the presence of TLS, which independently predicts PFS in both HGSOC patients and immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients. Overall, we reveal that TLS coordinates intratumoral B cell and T cell response to HGSOC tumor, while the cancer genome evolves to counteract TLS formation and function.

Thermal conductivity of glasses: first-principles theory and applications.

Predicting the thermal conductivity of glasses from first principles has hitherto been a very complex problem. The established Allen-Feldman and Green-Kubo approaches employ approximations with limited validity-the former neglects anharmonicity, the latter misses the quantum Bose-Einstein statistics of vibrations-and require atomistic models that are very challenging for first-principles methods. Here, we present a protocol to determine from first principles the thermal conductivity κ(T) of glasses above the plateau (i.e., above the temperature-independent region appearing almost without exceptions in the κ(T) of all glasses at cryogenic temperatures). The protocol combines the Wigner formulation of thermal transport with convergence-acceleration techniques, and accounts comprehensively for the effects of structural disorder, anharmonicity, and Bose-Einstein statistics. We validate this approach in vitreous silica, showing that models containing less than 200 atoms can already reproduce κ(T) in the macroscopic limit. We discuss the effects of anharmonicity and the mechanisms determining the trend of κ(T) at high temperature, reproducing experiments at temperatures where radiative effects remain negligible.

Electron-Phonon Interaction and Longitudinal-Transverse Phonon Splitting in Doped Semiconductors.

We study the effect of doping on the electron-phonon interaction and on the phonon frequencies in doped semiconductors, taking into account the screening in the presence of free carriers at finite temperature. We study the impact of screening on the Fröhlich-like vertex and on the long-range components of the dynamical matrix, going beyond the state-of-the-art description for undoped crystals, thanks to the development of a computational method based on maximally localized Wannier functions. We apply our approach to cubic silicon carbide, where in the presence of doping the Fröhlich coupling and the longitudinal-transverse phonon splitting are strongly reduced, thereby influencing observable properties such as the electronic lifetime.

Epigenetic potentiation of somatostatin-2 by guadecitabine in neuroendocrine neoplasias as a novel method to allow delivery of peptide receptor radiotherapy.

BACKGROUND: Somatostatin receptor-2 (SSTR2) is expressed on cell surface of neuroendocrine neoplasias; its presence is exploited for the delivery of peptide receptor radionuclide therapy (PRRT). Patients with no or low expression of SSTR2 are not candidates for PRRT. SSTR2 promotor undergoes epigenetic modification, known to regulate gene expression. We investigated whether the demethylation agent, guadecitabine, could enhance the expression of SSTR2 in NET models, using radioligand uptake/PET imaging as a biomarker of epigenetic modification. METHODS: The effects of guadecitabine on the transcriptional, translational, and functional regulation of SSTR2 both in vitro and in vivo using low (QGP-1) and high (BON-1) methylated neuroendocrine neoplasia models was characterised. Promotor region methylation profiling of clinical samples (n = 61) was undertaken. Safety of combination guadecitabine and PRRT was assessed in vivo. RESULTS: Pyrosequencing of cell lines illustrated differential methylation indices - BON: 1 94%, QGP: 1 21%. Following guadecitabine treatment, a dose-dependent increase in SSTR2 in BON-1 at a transcriptional, translational, and functional levels using the SSTR2-directed radioligand, 18F-FET-ßAG-TOCA ([18F]-FETO) (150% increase [18F]-FETO uptake, p < 0.05) was observed. In vivo, guadecitabine treatment resulted in a 70% increase in [18F]-FETO uptake in BON-1 tumour models compared models with low baseline percentage methylation (p < 0.05). No additive toxicity was observed with the combination treatment of PRRT and guadecitabine in vivo. Methylation index in clinical samples was 10.5% compared to 5.2% in controls (p = 0.03) and correlated with SSTR2 expression (Wilcoxon rank sign -3.75,p < 0.01). CONCLUSION: Guadecitabine increases SSTR2 expression both in vitro and in vivo. The combination of demethylation agents with PRRT warrants further investigation.

Gate-Tunable Magnetism and Giant Magnetoresistance in Suspended Rhombohedral-Stacked Few-Layer Graphene.

Conventionally, magnetism arises from the strong exchange interaction among the magnetic moments of d- or f-shell electrons. It can also emerge in perfect lattices from nonmagnetic elements, such as that exemplified by the Stoner criterion. Here we report tunable magnetism in suspended rhombohedral-stacked few-layer graphene (r-FLG) devices with flat bands. At small doping levels (n ∼ 1011 cm-2), we observe prominent conductance hysteresis and giant magnetoconductance that exceeds 1000% as a function of magnetic fields. Both phenomena are tunable by density and temperature and disappear at n > 1012 cm-2 or T > 5 K. These results are confirmed by first-principles calculations, which indicate the formation of a half-metallic state in doped r-FLG, in which the magnetization is tunable by electric field. Our combined experimental and theoretical work demonstrate that magnetism and spin polarization, arising from the strong electronic interactions in flat bands, emerge in a system composed entirely of carbon atoms.

The microscopic origin of the anomalous isotopic properties of ice relies on the strong quantum anharmonic regime of atomic vibration.

Water ice is a unique material presenting intriguing physical properties, such as negative thermal expansion and anomalous volume isotope effect (VIE). They arise from the interplay between weak hydrogen bonds and nuclear quantum fluctuations, making theoretical calculations challenging. Here, we employ the stochastic self-consistent harmonic approximation to investigate how thermal and quantum fluctuations affect the physical properties of ice XI with ab initio accuracy. Regarding the anomalous VIE, our work reveals that quantum effects on hydrogen are so strong to be in a nonlinear regime: When progressively increasing the mass of hydrogen from protium to infinity (classical limit), the volume first expands and then contracts, with a maximum slightly above the mass of tritium. We observe an anharmonic renormalization of about 10% in the bending and stretching phonon frequencies probed in IR and Raman experiments. For the first time, we report an accurate comparison of the low-energy phonon dispersion with the experimental data, possible only thanks to high-level accuracy in the electronic correlation and nuclear quantum and thermal fluctuations, paving the way for the study of thermal transport in ice from first-principles and the simulation of ice under pressure.

Dominant Role of Quantum Anharmonicity in the Stability and Optical Properties of Infinite Linear Acetylenic Carbon Chains.

Carbyne, an infinite-length straight chain of carbon atoms, is supposed to undergo a second order phase transition from the metallic bond-symmetric cumulene (═C═C═)∞ toward the distorted insulating polyyne chain (-C≡C-)∞ displaying bond-length alternation. However, recent synthesis of ultra long carbon chains (∼6000 atoms, [Nat. Mater., 2016, 15, 634]) did not show any phase transition and detected only the polyyne phase, in agreement with previous experiments on capped finite carbon chains. Here, by performing first-principles calculations, we show that quantum-anharmonicity reduces the energy gain of the polyyne phase with respect to the cumulene one by 71%. The magnitude of the bond-length alternation increases by increasing temperature, in stark contrast with a second order phase transition, confining the cumulene-to-polyyne transition to extremely high and unphysical temperatures. Finally, we predict that a high temperature insulator-to-metal transition occurs in the polyyne phase confined in insulating nanotubes with sufficiently large dielectric constant due to a giant quantum-anharmonic bandgap renormalization.

Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.

BACKGROUND: Modulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment. METHODS: We profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T- (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163. RESULTS: We analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p<0.001) compared with T-. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed upregulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T-. CONCLUSIONS: TACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant upregulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumor microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.

Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer.

Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through x-ray structure determination and Markov transient and Deuterium exchange analyses, we identified the allosteric binding site and revealed how this compound blocks RSK4 kinase activation through binding to an allosteric site and mimicking a kinase autoinhibitory mechanism involving the RSK4's hydrophobic motif. Last, we show that patients undergoing chemotherapy and adhering to prophylactic levofloxacin in the large placebo-controlled randomized phase 3 SIGNIFICANT trial had significantly increased (P = 0.048) long-term overall survival times. Hence, we suggest that RSK4 inhibition may represent an effective therapeutic strategy for treating lung and bladder cancer.

Intrinsic Vibrational Angular Momentum from Nonadiabatic Effects in Noncollinear Magnetic Molecules.

We show that in noncollinear magnetic molecules, nonadiabatic (dynamical) effects due to the electron-vibron coupling are time-reversal symmetry breaking interactions for the vibrational field. Because the electronic wave function cannot be chosen as real in these molecules, a nonzero geometric vector potential (Berry connection) arises. As a result, an intrinsic nonzero vibrational angular momentum occurs even for nondegenerate modes and in the absence of external probes. The vibronic modes can then be seen as elementary quantum particles carrying a sizeable angular momentum. As a proof of concept, we demonstrate the magnitude of this topological effect by performing nonadiabatic first principles calculations on platinum clusters and by showing that these molecules host sizeable intrinsic phonon angular momenta comparable to the orbital electronic ones in itinerant ferromagnets.

The stochastic self-consistent harmonic approximation: calculating vibrational properties of materials with full quantum and anharmonic effects.

The efficient and accurate calculation of how ionic quantum and thermal fluctuations impact the free energy of a crystal, its atomic structure, and phonon spectrum is one of the main challenges of solid state physics, especially when strong anharmonicy invalidates any perturbative approach. To tackle this problem, we present the implementation on a modular Python code of the stochastic self-consistent harmonic approximation (SSCHA) method. This technique rigorously describes the full thermodynamics of crystals accounting for nuclear quantum and thermal anharmonic fluctuations. The approach requires the evaluation of the Born-Oppenheimer energy, as well as its derivatives with respect to ionic positions (forces) and cell parameters (stress tensor) in supercells, which can be provided, for instance, by first principles density-functional-theory codes. The method performs crystal geometry relaxation on the quantum free energy landscape, optimizing the free energy with respect to all degrees of freedom of the crystal structure. It can be used to determine the phase diagram of any crystal at finite temperature. It enables the calculation of phase boundaries for both first-order and second-order phase transitions from the Hessian of the free energy. Finally, the code can also compute the anharmonic phonon spectra, including the phonon linewidths, as well as phonon spectral functions. We review the theoretical framework of the SSCHA and its dynamical extension, making particular emphasis on the physical inter pretation of the variables present in the theory that can enlighten the comparison with any other anharmonic theory. A modular and flexible Python environment is used for the implementation, which allows for a clean interaction with other packages. We briefly present a toy-model calculation to illustrate the potential of the code. Several applications of the method in superconducting hydrides, charge-density-wave materials, and thermoelectric compounds are also reviewed.

Phenotypic Characteristics of the Tumour Microenvironment in Primary and Secondary Hepatocellular Carcinoma.

(1) Background: The intra-tumoural heterogeneity (ITH) of hepatocellular carcinoma (HCC) and its microenvironment (TME) across primary and secondary disease is poorly characterised. (2) Methods: Intra-tumoural (IT) and peri-tumoural (PT) staining of matched primary and secondary samples was conducted to evaluate the distribution of CD4+/FOXP3+ and CD8+/PD1+ T-cells. Samples underwent PD-L1/2 immunostaining, tumour mutational burden (TMB) evaluation, and high-resolution T-cell receptor (TCR) sequencing to derive T-cell clonality and targeted transcriptomics. (3) Results: We analysed 24 samples from matched primary (n = 11) and secondary (n = 13; 5 synchronous, 6 metachronous) deposits, 11 being extrahepatic (84.6%). IT CD8+ density was lower than PT in both primary (p = 0.005) and secondary deposits (p = 0.01), consistent with immune exclusion. PD-L1+ tumours displayed higher IT and PT CD8+/PD1+ cell density compared to PD-L1- (p < 0.05), and primary IT infiltrate was enriched in CD4+/FOXP3+ cells, compared to PT regions (p = 0.004). TCR-sequencing demonstrated enrichment of the top T-cell clonotype in secondary versus primary HCC (p = 0.02), without differences in overall productive clonality (p = 0.35). TMB was similar across primary versus secondary HCC (p = 0.95). While directed gene set analysis demonstrated the uniformity of transcriptional signatures of individual immune cell types, secondary deposits demonstrated higher COLEC12 (p = 0.004), CCL26 (p = 0.02), CD1E (p = 0.02) and CD36 (p = 0.03) expression with downregulation of CXCL1 (p = 0.03), suggesting differential regulation of innate immunity. (4) Conclusion: Immune exclusion is a defining feature of the HCC TME. Despite evidence of homogeneity in somatic TMB, secondary HCC is characterised by the expansion of a distinct T-cell clonotype and differential regulation of innate immune pathways.

Anomalous High-Temperature Superconductivity in YH6.

Pressure-stabilized hydrides are a new rapidly growing class of high-temperature superconductors, which is believed to be described within the conventional phonon-mediated mechanism of coupling. Here, the synthesis of one of the best-known high-TC superconductors-yttrium hexahydride I m 3 ¯ m -YH6 is reported, which displays a superconducting transition at ≈224 K at 166 GPa. The extrapolated upper critical magnetic field Bc2 (0) of YH6 is surprisingly high: 116-158 T, which is 2-2.5 times larger than the calculated value. A pronounced shift of TC in yttrium deuteride YD6 with the isotope coefficient 0.4 supports the phonon-assisted superconductivity. Current-voltage measurements show that the critical current IC and its density JC may exceed 1.75 A and 3500 A mm-2 at 4 K, respectively, which is higher than that of the commercial superconductors, such as NbTi and YBCO. The results of superconducting density functional theory (SCDFT) and anharmonic calculations, together with anomalously high critical magnetic field, suggest notable departures of the superconducting properties from the conventional Migdal-Eliashberg and Bardeen-Cooper-Schrieffer theories, and presence of an additional mechanism of superconductivity.

Transcriptional analysis of multiple ovarian cancer cohorts reveals prognostic and immunomodulatory consequences of ERV expression.

BACKGROUND: Endogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via the viral sensing machinery. Baseline expression of ERVs also occurs in cancer cells, though this process is poorly understood and previously unexplored in epithelial ovarian cancer (EOC). Here, the prognostic and immunomodulatory consequences of baseline ERV expression was assessed in EOC. METHODS: ERV expression was assessed using EOC transcriptional data from The Cancer Genome Atlas (TCGA) and from an independent cohort (Hammersmith Hospital, HH), as well as from untreated or DNMTi-treated EOC cell lines. Least absolute shrinkage and selection operator (LASSO) logistic regression defined an ERV expression score to predict patient prognosis. Immunohistochemistry (IHC) was conducted on the HH cohort. Combination of DNMTi treatment with γδ T cells was tested in vitro, using EOC cell lines and patient-derived tumor cells. RESULTS: ERV expression was found to define clinically relevant subsets of EOC patients. An ERV prognostic score was successfully generated in TCGA and validated in the independent cohort. In EOC patients from this cohort, a high ERV score was associated with better survival (log-rank p=0.0009) and correlated with infiltration of CD8+PD1+T cells (r=0.46, p=0.0001). In the TCGA dataset, a higher ERV score was found in BRCA1/2 mutant tumors, compared to wild type (p=0.015), while a lower ERV score was found in CCNE1 amplified tumors, compared to wild type (p=0.019). In vitro, baseline ERV expression dictates the level of ERV induction in response to DNMTi. Manipulation of an ERV expression threshold by DNMTi resulted in improved EOC cell killing by cytotoxic immune cells. CONCLUSIONS: These findings uncover the potential for baseline ERV expression to robustly inform EOC patient prognosis, influence tumor immune infiltration and affect antitumor immunity.

van der Waals driven anharmonic melting of the 3D charge density wave in VSe2.

Understanding of charge-density wave (CDW) phases is a main challenge in condensed matter due to their presence in high-Tc superconductors or transition metal dichalcogenides (TMDs). Among TMDs, the origin of the CDW in VSe2 remains highly debated. Here, by means of inelastic x-ray scattering and first-principles calculations, we show that the CDW transition is driven by the collapse at 110 K of an acoustic mode at qCDW = (2.25 0 0.7) r.l.u. The softening starts below 225 K and expands over a wide region of the Brillouin zone, identifying the electron-phonon interaction as the driving force of the CDW. This is supported by our calculations that determine a large momentum-dependence of the electron-phonon matrix-elements that peak at the CDW wave vector. Our first-principles anharmonic calculations reproduce the temperature dependence of the soft mode and the TCDW onset only when considering the out-of-plane van der Waals interactions, which reveal crucial for the melting of the CDW phase.