Epigenetic Repression of STING by MYC Promotes Immune Evasion and Resistance to Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer.

The MYC oncogene is frequently amplified in triple-negative breast cancer (TNBC). Here, we show that MYC suppression induces immune-related hallmark gene set expression and tumor-infiltrating T cells in MYC-hyperactivated TNBCs. Mechanistically, MYC repressed stimulator of interferon genes (STING) expression via direct binding to the STING1 enhancer region, resulting in downregulation of the T-cell chemokines CCL5, CXCL10, and CXCL11. In primary and metastatic TNBC cohorts, tumors with high MYC expression or activity exhibited low STING expression. Using a CRISPR-mediated enhancer perturbation approach, we demonstrated that MYC-driven immune evasion is mediated by STING repression. STING repression induced resistance to PD-L1 blockade in mouse models of TNBC. Finally, a small-molecule inhibitor of MYC combined with PD-L1 blockade elicited a durable response in immune-cold TNBC with high MYC expression, suggesting a strategy to restore PD-L1 inhibitor sensitivity in MYC-overexpressing TNBC.

A Single-Center Trial to Evaluate the Efficacy and Tolerability of Four Microneedling Treatments on Fine Lines and Wrinkles of Facial and Neck Skin in Subjects With Fitzpatrick Skin Types I-IV: An Objective Assessment Using Noninvasive Devices and 0.33-mm Microbiopsies.

BACKGROUND: Although ablative techniques are the standard of care for the treatment of fine lines and wrinkles, microneedling offers a minimally invasive alternative. OBJECTIVES: The purpose of this study was to assess the efficacy of microneedling on facial and neck fine lines and wrinkles. METHODS: Thirty-five subjects between 44 and 65 years old with Fitzpatrick skin types I to IV received 4 monthly microneedling treatments over the face and neck. Subjects returned 1 and 3 months posttreatment. At every visit, high-resolution ultrasonography and optical coherence tomography were performed, and transepidermal water loss and skin elasticity were measured. Microbiopsies (0.33 mm) were collected pretreatment, before the fourth treatment and 3 months posttreatment. RESULTS: Thirty-two subjects (30 females, 2 males) completed all 7 visits. Facial dermal and epidermal density increased 101.86% and 19.28%, respectively, from baseline at 3 months posttreatment. Facial elasticity increased 28.2% from baseline at 3 months posttreatment. Facial attenuation coefficient increased 15.65% and 17.33% at 1 and 3 months posttreatment, respectively. At study completion, blood flow at a depth of 300 µm decreased 25.8% in the face and 42.3% in the neck. Relative collagen type III and elastin gene expression was statistically higher 3 months posttreatment. However, total elastin protein levels were unchanged from baseline values. Dermal muscle formation was observed in 58% of biopsies extracted 3 months posttreatment compared with 15.3% at baseline. CONCLUSIONS: The results illustrate the effects of microneedling treatments. Noninvasive measurements and biopsy data showed changes in skin architecture and collagen/elastin gene expression, suggesting skin rejuvenation, with new extracellular matrix production and muscle formation.