Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.

Fundamental Insights into Copper-Epoxy Interfaces for High-Frequency Chip-to-Chip Interconnects.

Future processes and materials are needed to enable multichip packages with chip-to-chip (C2C) data rates of 50 GB/s or higher. This presents a fundamental challenge because of the skin effect, which exacerbates signal transmission losses at high frequencies. Our results indicate that smooth copper interconnects with relatively thin cuprous oxides (CuO, Cu) and amine-functional silane adhesion promoters improve interfacial adhesion with epoxy dielectrics by nearly an order of magnitude.

Mapping intratumoral myeloid-T cell interactomes at single-cell resolution reveals targets for overcoming checkpoint inhibitor resistance.

Effective cancer immunotherapies restore anti-tumor immunity by rewiring cell-cell communication. Treatment-induced changes in communication can be inferred from single-cell RNA-sequencing (scRNA-seq) data, but current methods do not effectively manage heterogeneity within cell types. Here we developed a computational approach to efficiently analyze scRNA-seq-derived, single-cell-resolved cell-cell interactomes, which we applied to determine how agonistic CD40 (CD40ag) alters immune cell crosstalk alone, across tumor models, and in combination with immune checkpoint blockade (ICB).

Extending Copper Interconnects and Epoxy Dielectrics to Multi-GHz Frequencies.

Future multichip packages require Die-to-Die (D2D) interconnects operating at frequencies above 10 GHz; however, the extension of copper interconnects and epoxy dielectrics presents a trade-off between performance and reliability. This paper explores insertion losses and adhesion as a function of interface roughness at frequencies up to 18 GHz. We probe epoxy surface chemistry as a function of curing time and use wet etching to modulate surface roughness.