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Z-DNA Triggering Drug Kills Immunotherapy Resistant Melanoma by Mimicking Flu

A candidate drug triggers Z-DNA conformations in cells that in turn activates a highly immunogenic programmed pathway of inflammatory cell death in cancer-associated fibroblasts. In mouse studies, researchers showed that the compound (CBL0137), a member of the curaxin family, rekindles immune responses against melanoma resistant to immune checkpoint blockade immunotherapy by mimicking influenza infections. Combining a "virus mimetic" immune adjuvant with immunotherapy may rekindle an immune response in otherwise unresponsive patients.

Gut Microbes Signal Response to Immune Therapy in Melanoma

Scientists identify gut microbes associated with toxicity to combined checkpoint inhibitors in melanoma patients providing potential biomarkers for toxicity and treatment response. They also identify genomic and immune markers associated with combined immune therapy induced intestinal inflammation. The study investigates a potential new strategy to treat toxicity while maintaining response to combined immune checkpoint blockade through either IL-1R inhibition or manipulation of gut microbiota.

Single-Cell Insights on Inaccessible Tumor Environments Expand Therapeutic Options

Scientists at the Moffitt Cancer Center & Research Institute compare the immune landscapes of leptomeningeal melanoma metastases (LMM) and melanoma brain metastases (MBM) using single-cell RNA-seq, identifying key differences in the tumor microenvironment that may result in the development of improved therapeutics.