T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10.

Despite recent advances in cancer immunotherapy, certain tumor types, such as Glioblastomas, are highly resistant due to their tumor microenvironment disabling the anti-tumor immune response. Here we show, by applying an in-silico multidimensional model integrating spatially resolved and single-cell gene expression data of 45,615 immune cells from 12 tumor samples, that a subset of Interleukin-10-releasing HMOX1 myeloid cells, spatially localizing to mesenchymal-like tumor regions, drive T-cell exhaustion and thus contribute to the immunosuppressive tumor microenvironment. These findings are validated using a human ex-vivo neocortical glioblastoma model inoculated with patient derived peripheral T-cells to simulate the immune compartment.

Inhibition of metabotropic glutamate receptor III facilitates sensitization to alkylating chemotherapeutics in glioblastoma.

Glioblastoma (GBM), the most malignant tumor of the central nervous system, is marked by its dynamic response to microenvironmental niches. In particular, this cellular plasticity contributes to the development of an immediate resistance during tumor treatment. Novel insights into the developmental trajectory exhibited by GBM show a strong capability to respond to its microenvironment by clonal selection of specific phenotypes.

Meclofenamate causes loss of cellular tethering and decoupling of functional networks in glioblastoma.

Background: Glioblastoma cells assemble to a syncytial communicating network based on tumor microtubes (TMs) as ultra-long membrane protrusions. The relationship between network architecture and transcriptional profile remains poorly investigated. Drugs that interfere with this syncytial connectivity such as meclofenamate (MFA) may be highly attractive for glioblastoma therapy.

Probing different spin states in xylyl radicals and ions.

Resonant one-color two-photon ionization spectroscopy and mass-selected threshold photoelectron spectroscopy were applied to study the electronic doublet states of the three xylyl (methyl-benzyl) radicals above 3.9 eV as well as the singlet and triplet states of the cations up to 10.5 eV.

Perspective: C and laboratory spectroscopy related to diffuse interstellar bands.

In the last 30 years, our research has focused on laboratory measurements of the electronic spectra of organic radicals and ions. Many of the species investigated were selected based on their potential astrophysical relevance, particularly in connection with the identification of appealing candidate molecules for the diffuse interstellar absorptions. Notably, carbon chains and derivatives containing hydrogen and nitrogen atoms in their neutral and ionic forms were studied.

Fullerenes in Space.

In 1985 the football structure of C , buckminsterfullerene was proposed and subsequently confirmed following its macroscopic synthesis in 1990. From the very beginning the role of C and C in space was considered, particularly in the context of the enigmatic diffuse interstellar bands. These are absorption features found in the spectra of reddened star light.

Structure and Electronic Transitions of CHO and CHO Ions: Neon Matrix and Theoretical Studies.

CHO and CHO ions and the respective neutrals have been investigated by absorption spectroscopy in neon matrixes following mass selection of ions produced from salicylic acid. Three electronic transitions starting at 649.6, 431.

Pathway to the identification of C60+ in diffuse interstellar clouds.

The origin of the attenuation of starlight in diffuse clouds in interstellar space at specific wavelengths ranging from the visible to the near-infrared has been unknown since the first astronomical observations around a century ago. The absorption features, termed the diffuse interstellar bands, have subsequently been the subject of much research. Earlier this year four of these interstellar bands were shown to be due to the absorption by cold, gas phase [Formula: see text] molecules.

Electronic transitions of C5H(+) and C5H: neon matrix and CASPT2 studies.

Two electronic transitions at 512.3 and 250 nm of linear-C5H(+) are detected following mass-selective deposition of m/z = 61 cations into a 6 K neon matrix and assigned to the 1 (1)Π←X (1)Σ(+) and 1 (1)Σ(+)←X (1)Σ(+) systems. Five absorption systems of l-C5H with origin bands at 528,7, 482.

Electronic Characterization of Reaction Intermediates: The Fluorenylium, Phenalenylium, and Benz[f]indenylium Cations and Their Radicals.

Three vibrationally resolved absorption systems commencing at 538, 518, and 392 nm were detected in a 6 K neon matrix after mass-selected deposition of C13 H9 (+) ions (m/z=165) produced from fluorene in a hot-cathode discharge ion source. The benz[f]indenylium (BfI(+) : 538 nm), fluorenylium (FL9(+) : 518 nm), and phenalenylium (PHL(+) : 392 nm) cations are the absorbing molecules. Two electronic systems corresponding to neutral species are apparent at 490 and 546 nm after irradiation of the matrix with λ<260 nm photons and were assigned to the FL9 and BfI radicals, respectively.

Electronic Spectra of Protonated Fluoranthene in a Neon Matrix and Gas Phase at 10 K.

Four electronic systems with origin bands at 759.5, 559.3, 476.

The Electronic Spectrum of the Fulvenallenyl Radical.

The fulvenallenyl radical was produced in 6 K neon matrices after mass-selective deposition of C7H5(-) and C7H5(+) generated from organic precursors in a hot cathode ion source. Absorption bands commencing at λ=401.3 nm were detected as a result of photodetachment of electrons from the deposited C7H5(-) and also by neutralization of C7H5(+) in the matrix.

Gas Phase Detection of Benzocyclopropenyl.

The gas phase detection of benzocyclopropenyl is reported. In this aromatic resonance stabilized radical, a large angular strain is present due to a three-membered ring annelated to a benzene. The resonant two-color two-photon ionization technique is used to record the D1((2)A2) ← D0((2)B1) electronic transition of this radical after the in situ synthesis in a discharge source.

Electronic spectra of oxygen containing polycyclic hydrocarbon cations and the protonated analogues.

The electronic transitions of 9-fluorenone FL(+) and 2,3,6,7-dibenzotropone DBT(+) cations were detected in 6 K neon matrices following a mass-selective deposition. The absorptions at 649.2 and 472.

Electronic Spectroscopy of Resonantly Stabilized Aromatic Radicals: 1-Indanyl and Methyl Substituted Analogues.

The gas-phase electronic spectra of two resonantly stabilized radicals, 1-indanyl (C9H9) and 1-methyl-1-indanyl (C10H11), have been recorded in the visible region using a resonant two-color two-photon ionization (R2C2PI) scheme. The D1(A″) ← D0(A″) origin bands of 1-indanyl and 1-methyl-1-indanyl radicals are observed at 21157 and 20565 cm(–1), respectively. The excitation of a′ vibrations in the D1 state is observed up to ∼1500 cm(–1) above the origin band in both cases.

Laboratory confirmation of C60(+) as the carrier of two diffuse interstellar bands.

The diffuse interstellar bands are absorption lines seen towards reddened stars. None of the molecules responsible for these bands have been conclusively identified. Two bands at 9,632 ångströms and 9,577 ångströms were reported in 1994, and were suggested to arise from C60(+) molecules (ref.

Electronic spectra of linear HC5H and cumulene carbene H2C5.

The 1(3)Σu (-)←X(3)Σg (-) transition of linear HC5H (A) has been observed in a neon matrix and gas phase. The assignment is based on mass-selective experiments, extrapolation of previous results of the longer HC2n+1H homologues, and density functional and multi-state CASPT2 theoretical methods. Another band system starting at 303 nm in neon is assigned as the 1(1)A1←X˜(1)A1 transition of the cumulene carbene pentatetraenylidene H2C5 (B).

Electronic absorption spectra of H₂C₆O⁺ isomers: produced by ion-molecule reactions.

Three absorption systems with origins at 354, 497, and 528 nm were detected after mass-selected deposition of H2C6O(+) in a 6 K neon matrix. The ions were formed by the reaction of C2O with HC4H(+) in a mixture of C3O2 and diacetylene in a hot cathode source, or by dissociative ionization of tetrabromocyclohexadienone. The 497 and 354 nm systems are assigned to the 1(2)A″ ← X(2)A″ and 2(2)A″ ← X(2)A″ electronic transitions of B(+), (2-ethynylcycloallyl)methanone cation, and the 528 nm absorption to the 1(2)A2 ← X(2)B1 transition of F(+), 2-ethynylbut-3-yn-1-enone-1-ylide, on the basis of calculated excitation energies with CASPT2.

Gas-phase electronic transitions of C₁₇H₁₂N⁺ at 15 K.

The electronic spectrum of C17H12N(+), phenanthrene with a side chain, was measured in the gas phase at a vibrational and rotational temperature of ∼15 K in an ion trap using a resonant multiphoton dissociation technique. The C17H12N(+) structure was produced in a chemical ionization source and identified by a comparison with theoretical calculations of stable structures and excitation energies. The (3), (2), (1) (1)A ← X (1)A electronic transitions of this nitrogen-containing aromatic species with 30 atoms have origin band maxima at 23,586 ± 1 cm(-1), 16,120 ± 50 cm(-1), and 14,519 ± 30 cm(-1).

Electronic transitions of C₅H₃⁺ and C₅H₃: neon matrix and CASPT2 studies.

Two absorption systems of C5H3(+) starting at 350 and 345 nm were detected following mass-selective deposition of m/e = 63 ions in a 6 K neon matrix. These are assigned to the 1 (1)A1 ← X (1)A1 electronic transition of 1,2,3,4-pentatetraenylium H2CCCCCH(+) (isomer B(+)) and 1 (1)B2 ← X (1)A1 of penta-1,4-diyne-3-ylium HCCCHCCH(+) (C(+)). The absorptions of neutral C5H3 isomers with onsets at 434.

Laboratory spectroscopy of astrophysically relevant carbon species.

Carbon is one of the most common elements in the solar system, with a fractional abundance of 10(-4) relative to hydrogen. Thus, it is not surprising that over 100 carbon-bearing species have been definitively detected in the interstellar medium via their rotational, infrared, and/or electronic transitions. In order to identify these species, laboratory spectra are needed for comparison to astronomical data.

(1) (1)A' ← X (1)A' Electronic Transition of Protonated Coronene at 15 K.

The electronic spectrum of protonated coronene in the gas phase was measured at vibrational and rotational temperatures of ∼15 K in a 22-pole ion trap. The (1) (1)A' ← X (1)A' electronic transition of this larger polycyclic aromatic hydrocarbon cation has an origin band maximum at 14 383.8 ± 0.

Spectroscopic characterization of C7H3(+) and C7H3˙: electronic absorption and fluorescence in 6 K neon matrices.

Mass selective deposition of C7H3(+) (m/z = 87) into solid neon reveals the 1(1)A1←X(1)A1 electronic absorption system of hepta-1,2,3,4,5,6-heptahexaenylium cation B(+) [H2CCCCCCCH](+) with an origin band at 441.3 nm, 1(1)A'←X(1)A' transition of 2,4-pentadiynylium,1-ethynyl cation C(+) [HCCCHCCCCH](+) starting at 414.6 nm and the 1(1)A1←X(1)A1 one of cyclopropenylium,1,3-butadiynyl cation A(+) [HCCCCC<(CH=CH)](+) with an onset at 322.

Gas phase electronic spectra of carbon chains C(n) (n = 6-9).

Ultraviolet electronic transitions of the linear carbon chains C6, C7, C8, and C9 were measured in the gas phase by a mass-resolved 1 + 1 resonant two-photon ionization technique using a picosecond laser. Broad absorptions with band maxima at 230.2 and 259.