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ObjectiveHepatocellular carcinoma (HCC) tumour microenvironment (TME) is highly complex with diverse cellular components organising into various functional units, cellular neighbourhoods (CNs). And we wanted to define CN of HCC while preserving the TME architecture, based on which, potential targets for novel immunotherapy could be identified.DesignA highly multiplexed imaging mass cytometry (IMC) panel was designed to simultaneously quantify 36 biomarkers of tissues from 134 patients with HCC and 7 healthy donors to generate 562 highly multiplexed histology images at single-cell resolution. Different function units were defined by topological analysis of TME. CN relevant to the patients’ prognosis was identified as specific target for HCC therapy. Transgenic mouse models were used to validate the novel immunotherapy target for HCC.ResultsThree major types of intratumour areas with distinct distribution patterns of tumorous, stromal and immune cells were identified. 22 cellular metaclusters and 16 CN were defined. CN composed of various types of cells formed regional function units and the regional immunity was regulated reversely by resident Kupffer cells and infiltrating macrophages with protumour and antitumour function, respectively. Depletion of Kupffer cells in mouse liver largely enhances the T cell response, reduces liver tumour growth and sensitises the tumour response to antiprogrammed cell death protein-1 treatment.ConclusionOur findings reveal for the first time the various topological function units of HCC TME, which also presents the largest depository of pathological landscape for HCC. This work highlights the potential of Kupffer cell-specific targeting rather than overall myeloid cell blocking as a novel immunotherapy for HCC treatment.

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Using, urea, one of the cheapest chemicals and convenient deamination polycondensation (solvent-free, catalyst-free, one-pot, one-step) provides an industrially relevant and environmentally benign synthesis of branched polyurea. Inspired by the structural analysis of traditional resin adhesives, we hypothesized that the higher the cross-linking degree of the adhesive after curing, the better the bonding performance. Improving the branching cross-linking degree of resin adhesives is the key to improve their bonding performance. In this work, in order to verify the relationship between the branching degree of the polymer adhesives and their bonding properties, branched polyureas with different branching degrees were designed and synthesized. Five polyamines of PA4N, PA5N, PA6N‑1, PA6N‑2, and PA7N were synthesized from ethylenediamine, diethylenetriamine, tris­(2-aminoethyl)­amine, triethylenetetramine, and tetraethylenepentamine, respectively. Polycondensation of urea with polyamine (PA4N, PA5N, PA6N‑1, PA6N‑2, and PA7N) by deamination achieved branched polyureas including PA4N–urea, PA5N–urea, PA6N‑1–urea, PA6N‑2–urea, and PA7N–urea via a solvent-free, catalyst-free, one-pot, and one-step approach. The polyureas were detailedly investigated as robust adhesives for wood bonding. The bonding performance of the branched polyureas, including PA4N–urea, PA5N–urea, PA6N‑1–urea, PA6N‑2–urea, and PA7N–urea, was represented by lap shear strengths of 1.52, 2.08, 2.23, 2.36, and 2.64 MPa for poplar wood after soaking the specimens in boiling water for 3.0 h, respectively, which indicated the superior lap shear strength and enhanced water resistance for use as a wood adhesive. As we expected, the results showed that the bonding strength of branched polyurea increased with an increase of the number of terminal functional groups. Besides, the adhesive performance on other substrates, including glass, aluminum, stainless steel, and polyvinyl chloride, was also studied, and the adhesion strengths to glass, aluminum, stainless steel, and polyvinyl chloride are 3.52, 3.29, 1.45, and 1.25 MPa, respectively.