USD Magazine Winter 1995 10.2

Letter From The Editor; Contents; Alcala Almanac; At Center Stage; Dear Mr. O\u27Brien; Blueprint for the Future; Alumni Gallery; Kaleidoscope; Parting Shothttps://digital.sandiego.edu/usdmagazine/1007/thumbnail.jp

Prognostic Significance of Interferon-γ and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes

Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype-specific prognostic significance of interferon-γ (IFN-γ) as a single gene as well as an IFN-γ signature covering the signaling pathway in 461 breast cancer patients. Prognostic significance of IFN-γ, as well as the IFN-γ signature for metastasis-free survival (MFS), were examined using Kaplan–Meier as well as univariate and multivariate Cox regression analyses in the whole cohort and in different molecular subtypes. The independent prognostic significance of IFN-γ as a single gene was limited to basal-like breast cancer (hazard ratio (HR) 2.779, 95% confidence interval (95% CI) 1.117–6.919, p = 0.028). In contrast, the IFN-γ-associated gene signature was an independent prognostic factor in the whole cohort (HR 2.287, 95% CI 1.410–3.633, p < 0.001) as well as in the basal-like (HR 3.458, 95% CI 1.154–10.359, p = 0.027) and luminal B (HR 2.690, 95% CI 1.416–5.112, p = 0.003) molecular subtypes. These results underline the subtype-dependent prognostic influence of the immune system in early breast cancer

Microglial A20 protects the brain from CD8 T-cell-mediated immunopathology

Tumor-necrosis-factor-alpha-induced protein 3 (TNFAIP3), or A20, is a ubiquitin-modifying protein and negative regulator of canonical nuclear factor κB (NF-κB) signaling. Several single-nucleotide polymorphisms in TNFAIP3 are associated with autoimmune diseases, suggesting a role in tissue inflammation. While the role of A20 in peripheral immune cells has been well investigated, less is known about its role in the central nervous system (CNS). Here, we show that microglial A20 is crucial for maintaining brain homeostasis. Without microglial A20, CD8+ T cells spontaneously infiltrate the CNS and acquire a viral response signature. The combination of infiltrating CD8+ T cells and activated A20-deficient microglia leads to an increase in VGLUT1+ terminals and frequency of spontaneous excitatory currents. Ultimately, A20-deficient microglia upregulate genes associated with the antiviral response and neurodegenerative diseases. Together, our data suggest that microglial A20 acts as a sensor for viral infection and a master regulator of CNS homeostasis