MHC1/LILRB1 axis as an innate immune checkpoint for cancer therapy.

Immune checkpoint blockades (ICBs) have revolutionized cancer therapy through unleashing anti-tumor adaptive immunity. Despite that, they are usually effective only in a small subset of patients and relapse can occur in patients who initially respond to the treatment. Recent breakthroughs in this field have identified innate immune checkpoints harnessed by cancer cells to escape immunosurveillance from innate immunity. MHC1 appears to be such a molecule expressed on cancer cells which can transmit a negative signal to innate immune cells through interaction with leukocyte immunoglobulin like receptor B1 (LILRB1). The review aims to summarize the current understanding of MHC1/LILRB1 axis on mediating cancer immune evasion with an emphasis on the therapeutic potential to block this axis for cancer therapy. Nevertheless, one should note that this field is still in its infancy and more studies are warranted to further verify the effectiveness and safety in clinical as well as the potential to combine with existing immune checkpoints.

1H, 13C, 15N backbone and side-chain resonance assignments of the pathogenic G131V mutant of human prion protein (91-231).

Human prion disease, also known as transmissible spongiform encephalopathy (TSEs), is caused by the conformational conversion of the normal cellular prion protein (PrPC) into the scrapie form (PrPSc). Pathogenic point mutations of prion proteins typically facilitate conformational conversion and lead to inherited prion diseases. A previous study has demonstrated that the pathogenic G131V mutation of human prion protein (HuPrP) brings in Gerstmann-Sträussler-Scheinker syndrome. However, the three-dimensional structure and dynamic features of the HuPrP(G131V) mutant remain unclear. It is expected that the determination of these structural bases will be beneficial to the pathogenic mechanistic understanding of G131V-related prion diseases. Here, we performed 1H, 15N, 13C backbone and side-chain resonance assignments of the G131V mutant of HuPrP(91-231) by using heteronuclear multi-dimensional NMR spectroscopy, and predicted the secondary structural elements and order parameters of the protein based on the assigned backbone chemical shifts. Our work lays the necessary foundation for further structural determination, dynamics characterization, and intermolecular interaction assay for the G131V mutant.