Genomic and immune characteristics of HER2-mutated non-small-cell lung cancer and response to immune checkpoint inhibitor-based therapy.

The efficacy of immunotherapy in advanced HER2-mutated non-small-cell lung cancer (NSCLC) remains incomprehensively studied. A total of 107 NSCLC patients with de novo HER2 mutations were retrospectively studied at Guangdong Lung Cancer Institute [GLCI cohort, exon 20 insertions (ex20ins): 71.0%] to compare clinical/molecular features and immune checkpoint inhibitor (ICI)-based therapy efficacy between patients with ex20ins and non-ex20ins. Two external cohorts (TCGA, n = 21; META-ICI, n = 30) were used for validation. In the GLCI cohort, 68.2% of patients displayed programmed death-ligand 1 (PD-L1) expression < 1%. Compared with ex20ins patients, non-ex20ins patients had more concurrent mutations in the GLCI cohort (P < 0.01) and a higher tumour mutation burden in the TCGA cohort (P = 0.03). Under ICI-based therapy, advanced NSCLC patients with non-ex20ins had potentially superior progression-free survival [median: 13.0 vs. 3.6 months, adjusted hazard ratio (HR): 0.31, 95% confidence interval (CI): 0.11-0.83] and overall survival (median: 27.5 vs. 8.1 months, adjusted HR: 0.39, 95% CI: 0.13-1.18) to ex20ins patients, consistent with findings in the META-ICI cohort. ICI-based therapy may serve as an option for advanced HER2-mutated NSCLC, with potentially better efficacy in non-ex20ins patients. Further investigations are warranted in clinical practice.

Comparative Study on Immune Function of the Head and Trunk Kidney in Rainbow Trout Responding to IHNV Infection.

A teleost's kidney was divided into head kidney and trunk kidney. The head kidney is an important lymphatic organ, while the trunk kidney mainly performs osmotic pressure regulation and excretion functions. Previous studies have shown that the teleost's head kidney exerts a strong immune response against pathogen invasion, while the mechanism of immune response in the trunk kidney is still rarely reported. Therefore, in this study, we established an Infectious hematopoietic necrosis virus (IHNV) immersion infection model to compare the similarities and differences of immune response mechanisms between the head kidney and trunk kidney against viral infection. The results showed that IHNV infection causes severe tissue damage and inflammatory reaction in the head and trunk kidney, triggers a series of interferon cascade reactions, and produces strong immune response. In addition, the transcriptome data showed that the head kidney and trunk kidney had similar immune response mechanisms, which showed that the NOD-like receptor signaling pathway and Toll-like receptor signaling pathway were activated. In conclusion, despite functional differentiation, the teleost's trunk kidney still has a strong immune response, especially the interferon-stimulated genes, which have stronger immune response in the trunk kidney than in the head kidney when responding to IHNV infection. This study contributes to a more comprehensive understanding of the teleost immune system and enriches the theory of kidney immunity in teleosts.

Blood brain barrier permeability and immune function of brain in rainbow trout responding to IHNV infection.

Viral infection of the central nervous system (CNS) is often associated with blood-brain barrier (BBB) disruption. Mammals have developed complicated and efficient immune strategies to protect the BBB. However, the immune defense of brain and BBB permeability changes are not well-understood in teleost during virus invading. In this study, we constructed an infectious hematopoietic necrosis virus (IHNV) immersion infected rainbow trout model. After IHNV infection, pathological changes occurred in the brain, and MPO and ROS activities were significantly increased. In addition, the expression levels of BBB permeability-related genes were also changed. Transcriptome analysis showed that immune-related genes and signaling pathways in the brain were activated after IHNV infection. These results showed that the permeability of BBB increased significantly after IHNV infection, thus activating immune related factors and cells to enter the CNS through blood circulation to resist pathogenic infection.

[Expression and clinical significance of the genes of Wnt signaling pathway in keratocystic odontogenic tumor of the jaw bones].

PURPOSE: To study the role of genes of Wnt signaling pathway in keratocystic odontogenic tumor (KCOT) of the jaw bones. METHODS: Fresh specimens of KCOT and the same patient 's normal oral mucosa were obtained. Then RNA was extracted. Gene chip was used to detect the genes of Wnt signaling pathway. RESULTS: Compared to normal oral mucosa, there were 5 genes of Wnt signaling pathway in KCOT changed, including CAMK2A down-regulated, FZD3, MAPK10, PRKX and WNT5a up-regulated. CONCLUSIONS: There are abnormal expressions of genes of Wnt pathway in KCOT. Genes of Wnt pathway plays certain roles in KCOT.