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PNAS Papers on Infection-Related CNS Inflammation, Cancer Clues in Blood Immune Features, More

University of Iowa researchers explore the roots of ongoing central nervous system (CNS) inflammation in mouse models infected with a nervous system-attacking betacoronavirus called mouse hepatitis virus (MHV), which produces acute and chronic demyelinating symptoms similar to those found in humans with multiple sclerosis. With the help of a recombinant version of MHV expressing a fluorescent protein, the team did lineage tracing in mice with acute infections, demonstrating that inflammatory gene-expressing oligodendrocytes and oligodendrocyte precursors tend to persist for months after infection in parts of the CNS that undergo demyelination. These and other findings suggest oligodendrocytes "are inducers as well as targets of the host immune response," the authors report, "and demonstrate how a CNS infection, even after resolution, can induce prolonged inflammatory changes with CNS region-dependent impairment in remyelination."

A team from the City of Hope National Medical Center and elsewhere tracks circulating immune cell features in relation to immune cell interactions found in advanced gastrointestinal tumors for another paper in PNAS. The researchers relied on single-cell RNA sequencing, in combination with clinical data and population modeling, to profile circulating immune cell patterns in more than a dozen individuals with advanced colorectal, gastroesophageal, pancreatic, or biliary cancer who did or did not respond to chemotherapy and anti-PD-1 immunotherapy treatment in a Phase I clinical trial of the drug combination. "This combination of mathematical modeling and genomic analyses suggests that peripheral blood immune cell phenotypes reflect cancer-immune cell interactions," they write, "and can reliably reveal patient responsiveness to immunotherapy."

Investigators in Sweden, Pakistan, and Ukraine describe roles for the mitochondrial ribosomal protein S18-2 and the retinoblastoma-associated protein RB in cell "stemness" in a experiments done on primary mouse embryonic fibroblasts, developing zebrafish, and a human mesenchymal stem cell line. In a series of knockdown, interaction, expression, and other analyses, the team teased out S18-2 and RB interactions and their contributions to cells' ability to renew themselves and differentiate, along with potential ties to tumor growth. "Collectively," the authors report, "our findings suggest an important role for S18-2 in cell stemness and differentiation and potentially also in cancerogenesis."