Developing plasmonic biosensors that are low‐cost, portable, and relatively simple to operate remains challenging. Herein, a novel metasurface plasmon‐etch immunosensor is described, namely a nanozyme‐linked immunosorbent surface plasmon resonance biosensor, for the ultrasensitive and specific detection of cancer biomarkers. Gold‐silver composite nano cup array metasurface plasmon resonance chip and artificial nanozyme‐labeled antibody are used in two‐way sandwich analyte detection. Changes in the biosensor's absorption spectrum are measured before and after chip surface etching, which can be applied to immunoassays without requiring separation or amplification. The device achieved a limit of alpha‐fetoprotein (AFP) detection < 21.74 fM, three orders of magnitude lower than that of commercial enzyme‐linked immunosorbent assay kits. Additionally, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) are used for quantitative detection to verify the universality of the platform. More importantly, the accuracy of the platform is verified using 60 clinical samples; compared with the hospital results, the three biomarkers achieve high sensitivity (CEA: 95.7%; CA125: 90.9%; AFP: 86.7%) and specificity (CEA: 97.3%; CA125: 93.9%; AFP: 97.8%). Due to its rapidity, ease of use, and high throughput, the platform has the potential for high‐throughput rapid detection to facilitate cancer screening or early diagnostic testing in biosensing.

Therapeutic blockade of the immune checkpoint proteins programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has transformed cancer treatment. However, the overall response rate to these treatments is low, suggesting that immune checkpoint activation is not the only mechanism leading to dysfunctional anti-tumour immunity. Here we show that butyrophilin-like protein 2 (BTNL2) is a potent suppressor of the anti-tumour immune response. Antibody-mediated blockade of BTNL2 attenuates tumour progression in multiple in vivo murine tumour models, resulting in prolonged survival of tumour-bearing mice. Mechanistically, BTNL2 interacts with local γδ T cell populations to promote IL-17A production in the tumour microenvironment. Inhibition of BTNL2 reduces the number of tumour-infiltrating IL-17A-producing γδ T cells and myeloid-derived suppressor cells, while facilitating cytotoxic CD8⁺ T cell accumulation. Furthermore, we find high BTNL2 expression in several human tumour samples from highly prevalent cancer types, which negatively correlates with overall patient survival. Thus, our results suggest that BTNL2 is a negative regulator of anti-tumour immunity and a potential target for cancer immunotherapy.

Significance: The B-cell–specific antibody gene-diversifying enzyme activation-induced cytidine deaminase (AID) shows high homology with apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1 (APOBEC1), which edits apolipoprotein B-100 mRNA in the presence of cofactor APOBEC1 complementation factor/APOBEC complementation factor (A1CF/ACF). Here we show that the DNA cleavage and recombination functions of AID depend critically on its RNA-dependent interaction with distinct heterogeneous nuclear ribonucleoprotein (hnRNP) cofactors. Depletion of hnRNP K inhibited DNA cleavage essential to both class switch recombination (CSR) and somatic hypermutation, but depletion of hnRNP L blocked the CSR-associated recombination. Thus this is the first report, to our knowledge, identifying A1CF-like hnRNP-family editing cofactors for AID.