Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma.

Background: Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NISSO study.

Methods: NISSO is an ongoing non-interventional, multinational, post-authorization safety study (NCT04066504).

Assessment of various efficacy outcomes using ERIVANCE-like criteria in patients with locally advanced basal cell carcinoma receiving sonidegib: results from a preplanned sensitivity analysis.

Background: The BOLT study for sonidegib, a Hedgehog pathway inhibitor (HHI) approved for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy, used modified Response Evaluation Criteria in Solid Tumors (mRECIST) for laBCC tumor evaluation. The ERIVANCE study for vismodegib, another HHI, used a composite RECIST endpoint of ≥30% reduction in externally visible tumor or radiographic dimension, or complete ulceration resolution. This preplanned sensitivity BOLT analysis evaluated efficacy outcomes using ERIVANCE-like criteria in patients with laBCC who received sonidegib 200 mg once daily.

Key Clinical Adverse Events in Patients with Advanced Basal Cell Carcinoma Treated with Sonidegib or Vismodegib: A Post Hoc Analysis.

Introduction: Sonidegib is approved to treat locally advanced basal cell carcinoma (laBCC) in the USA, EU, Switzerland, and Australia and metastatic basal cell carcinoma (mBCC) in Switzerland and Australia in patients not amenable to surgery or radiotherapy. Vismodegib is approved to treat patients with mBCC, recurrent laBCC, or those not candidates for surgery or radiation. There is no head-to-head trial comparing Hedgehog inhibitors.

Adaptive NKG2CCD57 Natural Killer Cell and Tim-3 Expression During Viral Infections.

Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions-a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection.

CD57 in human natural killer cells and T-lymphocytes.

The CD57 antigen (alternatively HNK-1, LEU-7, or L2) is routinely used to identify terminally differentiated 'senescent' cells with reduced proliferative capacity and altered functional properties. In this article, we review current understanding of the attributes of CD57-expressing T-cells and NK cells in both health and disease and discuss how this marker can inform researchers about their likely functions in human blood and tissues in vivo. While CD57 expression on human lymphocytes indicates an inability to proliferate, these cells also display high cytotoxic potential, and CD57(pos) NK cells exhibit both memory-like features and potent effector functions.

Compartmentalization of immunosenescence: a deeper look at the mucosa.

Developments in medical care and living conditions led to an astonishing increase in life-span perspective and subsequently a rise in the old population. This can be seen as a success for public health policies but it also challenges society to adapt, in order to cope with the potentially overwhelming cost for the healthcare system. A fast-growing number of older people lose their ability to live independently because of diseases and disabilities, frailty or cognitive impairment.