Daily Respiratory Research Analysis

To identify nasopharyngeal carcinoma (NPC)-relevant T cell receptors (TCRs), we profile the repertoires of peripheral blood TCRβ chains from 228 NPC patients, 241 at-risk controls positive for serum Epstein-Barr virus (EBV) VCA-IgA antibody, and 251 seronegative controls. We develop a TCR-based signature (T-score) based on 208 NPC-enriched CDR3β sequences, which accurately diagnoses NPC in both the original and independent validation cohorts. Notably, a higher T-score, associated with a shorter time interval to NPC diagnosis, effectively identifies early-stage NPC among EBV-seropositive at-risk individuals prior to clinical diagnosis. These NPC-enriched TCRs react against not only EBV-specific antigens but also non-EBV antigens expressed by NPC cells, indicating a broad range of specificities. Moreover, the abundance of NPC-enriched CD8

How tumor microenvironment shapes lung adenocarcinoma (LUAD) precancer evolution remains poorly understood. Spatial immune profiling of 114 human LUAD and LUAD precursors reveals a progressive increase of adaptive response and a relative decrease of innate immune response as LUAD precursors progress. The immune evasion features align the immune response patterns at various stages. TIM-3-high features are enriched in LUAD precancers, which decrease in later stages. Furthermore, single-cell RNA sequencing (scRNA-seq) and spatial immune and transcriptomics profiling of LUAD and LUAD precursor specimens from 5 mouse models validate high TIM-3 features in LUAD precancers. In vivo TIM-3 blockade at precancer stage, but not at advanced cancer stage, decreases tumor burden. Anti-TIM-3 treatment is associated with enhanced antigen presentation, T cell activation, and increased M1/M2 macrophage ratio. These results highlight the coordination of innate and adaptive immune response/evasion during LUAD precancer evolution and suggest TIM-3 as a potential target for LUAD precancer interception.

BACKGROUND: Myokine dysregulation and mitochondrial dysfunction are implicated in the pathogenesis of sarcopenia in chronic obstructive pulmonary disease. The objective of this study is to explore the role of myokines and mitochondrial dysfunction in sarcopenia in chronic obstructive pulmonary disease. METHODS: We identified mitsugumin 53 and its clinical correlation through an enzyme-linked immunosorbent assay using the plasma samples of patients with chronic obstructive pulmonary disease. The role of mitsugumin 53 was confirmed in mitsugumin 53-knockout mice. The underlying mechanisms were investigated using multi-omics sequencing, live-cell imaging, and histological and molecular experiments. The effectiveness and safety of recombinant mitsugumin 53 in treating cigarette smoke-induced muscle dysfunction were evaluated in vitro and in vivo. RESULTS: Plasma mitsugumin 53 levels were decreased in patients with chronic obstructive pulmonary disease and were associated with skeletal muscle dysfunction. Mitsugumin 53 deficiency exacerbated cigarette smoking-induced skeletal muscle atrophy. In muscle cells, mitsugumin 53 co-localized with the mitochondria and regulated mitochondrial fission. As a lipid transporter, mitsugumin 53 directly bound to the mitochondria-specific lipid cardiolipin and participated in maintaining mitochondrial homeostasis and membrane integrity. As an E3-ligase, mitsugumin 53 deletion triggered BCL2L13-mediated mitochondrial fission upon cigarette smoking stimulation. Supplementation with recombinant mitsugumin 53 significantly alleviated cigarette smoking-induced muscle atrophy and rescued mitochondrial dysfunction in vitro and in vivo. CONCLUSIONS: Mitsugumin 53 is a vital regulator of sarcopenia in patients with chronic obstructive pulmonary disease. Thus, mitsugumin 53 and mitochondrial fission may be promising therapeutic targets for muscle dysfunction in chronic obstructive pulmonary disease.