Evaluating the safety and efficacy of baricitinib for the treatment of moderate-to-severe atopic dermatitis.

INTRODUCTION: New biologic and small molecule therapeutics have emerged for the treatment of moderate-to-severe atopic dermatitis (AD), including oral Janus kinase (JAK) inhibitors such as baricitinib. While JAK inhibitors are commonly used to treat rheumatoid arthritis and inflammatory bowel disease, these agents are relatively new in the field of dermatology. AREAS COVERED: In this review, we outline the efficacy and safety data of phase III randomized controlled trials investigating the use of baricitinib for moderate-to-severe AD. A literature search was performed using PubMed.gov to identify articles relevant to the topic published before August 2023. EXPERT OPINION: Oral JAK inhibitors in AD management are highly efficacious, whether used alone, in conjunction with topical corticosteroids, or in patients who have failed other conventional systemic medications for AD. JAK inhibitors appear to be well tolerated in the AD patient population with fewer major safety risks than what has been seen in other patient populations. Assessing patient risk factors for cardiovascular, thromboembolic, and oncologic diseases is now an important part of the office visit for patients in whom you may consider using a JAK inhibitor.

Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer.

Chemotherapy prior to immune checkpoint blockade (ICB) treatment appears to improve ICB efficacy but resistance to ICB remains a clinical challenge and is attributed to highly plastic myeloid cells associating with the tumor immune microenvironment (TIME). Here we show by CITE-seq single-cell transcriptomic and trajectory analyses that neoadjuvant low-dose metronomic chemotherapy (MCT) leads to a characteristic co-evolution of divergent myeloid cell subsets in female triple-negative breast cancer (TNBC). Specifically, we identify that the proportion of CXCL16 + myeloid cells increase and a high STAT1 regulon activity distinguishes Programmed Death Ligand 1 (PD-L1) expressing immature myeloid cells. Chemical inhibition of STAT1 signaling in MCT-primed breast cancer sensitizes TNBC to ICB treatment, which underscores the STAT1's role in modulating TIME. In summary, we leverage single-cell analyses to dissect the cellular dynamics in the tumor microenvironment (TME) following neoadjuvant chemotherapy and provide a pre-clinical rationale for modulating STAT1 in combination with anti-PD-1 for TNBC patients.