Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.

Detrital Zircon U-Pb Geochronology from Greywackes in the Niujuanzi Ophiolitic Mélange, Beishan Area, NW China: Provenance and Tectonic Implications

The Niujuanzi ophiolitic m^lange represents the remnant of oceanic crust between the Dunhuang massif and Mingshui-Hanshan massif. Greywacke from different tectonic slices in the Niu- juanzi ophiolitic mdlange were analyzed for detrital zircon U-Pb geochronology, trace dements and whole-rock trace elements to infer their provenance and the evolution of the Niujuanzi Ocean. Sample N-76s containing Carboniferous spores has the youngest zircon age of 323 Ma, while sample N-85s without fossils has the youngest zircon age of 449 Ma. The two samples were deposited no earlier than 323 and 449 Ma, respectively. The greywackes are depleted in large ion lithophile elements, and are relatively enriched in high field strength elements. The age spectra and trace element concentrations indicate that the sediments may have been deposited near the trench. The Hf, U, and Yb contents of zircons from sample N-76s vary widely, whereas those from sample N-85s have a narrow range. Sample N-76s contains both continental and oceanic zircons, while sample N-85s contains only continental zir-cons. The sediments were derived from the continental arc and accretionary wedge. The Paleozoic oce- anic crust zircons have ages of 430-500 Ma, indicating the timing of the expansion of the Hongliuhe- Niujuanzi-Xichangjing Ocean expansion. The oldest Paleozoic continental zircon has an age of 470 Ma, suggesting that the northward subduction of the oceanic crust may have started at that time.

Regulating the dimensionality of diphosphaperylenediimide-based polymers by coordinating the out-of-plane anisotropic π-framework toward Ag^(+)

The development of hetero-π-conjugated molecules is of significance for constructing diverse assembling superstructures based on heteroatom-related bonded or nonbonded interactions.Herein,we developed one-pot P-heteroannulation via palladiumcatalyzed dual P-C bonds formation and subsequent sulfidation to construct two isomeric diphosphaperylenediimides(cis-5 and trans-5).The unique out-of-plane anisotropic π-framework induced a cumulative anisotropy with a dipole moment of up to 8.82 D for cis-5,leading to distinct supramolecular packing arrangements.Optical and electrochemical characterizations demonstrated that they showed the largest redshifts extending to 574 nm and rather low-lying LUMO levels of −4.41 eV.Furthermore,the introduced P=S moieties endowed these diphosphaperylenediimides with prominent coordination ability towards Ag^(+),and thus the first example of perylene diimide(PDI)core-involved metal-organic coordination polymers(MOCPs)with tunable dimensionality varying from 1D,2D,to 3D was tactfully achieved.In view of easy accessibility and 2D layered porous structure,thus 2D(trans-5)·(AgOTf)based MOCP showed high crystallinity and good CO_(2) adsorption capacity with surface area of 112 m^(2)/g.The result opens a span-new avenue for exploring rylene imide-based MOCPs and related properties by integrating P functionality.