Hair-to-Hair Trichoscopy: An Objective Method to Assess Effectiveness of Botulinum Toxin in a Clinical Trial for Androgenetic Alopecia.

Introduction: Androgenetic alopecia (AGA) is the most common alopecia affecting both genders leading to a potential decrease in quality of life and self-esteem. A current concern in trichology is how to accurately measure clinical response in both daily medical practice and academic research. Hair-to-hair (H2H)-matching technology™ has recently emerged as a technique to evaluate variations in follicular units, hair shaft number, and thickness.

The mitochondrial pyruvate carrier regulates memory T cell differentiation and antitumor function.

Glycolysis, including both lactate fermentation and pyruvate oxidation, orchestrates CD8 T cell differentiation. However, how mitochondrial pyruvate metabolism and uptake controlled by the mitochondrial pyruvate carrier (MPC) impact T cell function and fate remains elusive. We found that genetic deletion of MPC drives CD8 T cell differentiation toward a memory phenotype.

Bicalutamide and the new perspectives for female pattern hair loss treatment: What dermatologists should know.

Female pattern hair loss (FPHL) is the most common form of alopecia in women. FPHL may compromise body image and strongly affect self-esteem, negatively impacting quality of life. Currently, the only Food and Drug Administration (FDA) approved drug for its treatment is topical minoxidil, with a variable response rate.

Redirecting iNKT Cell Antitumor Immunity with α-GalCer/CD1d-scFv Fusion Proteins.

Invariant natural killer T (iNKT) cells display important properties that could bridge the innate and adaptive immunity, and they have been shown to play key roles in cancer immunotherapy. However, administration of iNKT cell agonist αGalCer fails to induce sustained antitumor immunity due to the rapid anergy induction after an initial strong activation. To this end, we have designed a recombinant CD1d protein that is fused to an anti-TAA scFv, which is able to recruit iNKT cells to the tumor site and induce tumor regression.

Serial Stimulation of Invariant Natural Killer T Cells with Covalently Stabilized Bispecific T-cell Engagers Generates Antitumor Immunity While Avoiding Anergy.

CD1d-restricted invariant natural killer T cells (iNKT cells) mediate strong antitumor immunity when stimulated by glycolipid agonists. However, attempts to develop effective iNKT cell agonists for clinical applications have been thwarted by potential problems with dose-limiting toxicity and by activation-induced iNKT cell anergy, which limits the efficacy of repeated administration. To overcome these issues, we developed a unique bispecific T-cell engager (BiTE) based on covalent conjugates of soluble CD1d with photoreactive analogues of the glycolipid α-galactosylceramide.

An Immunomodulatory Gallotanin-Rich Fraction From Enhances the Therapeutic Effect of Anti-PD-L1 in Melanoma.

PD-1/PD-L1 pathway plays a role in inhibiting immune response. Therapeutic antibodies aimed at blocking the PD-1/PD-L1 interaction have entered clinical development and have been approved for a variety of cancers. However, the clinical benefits are reduced to a group of patients.

Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity.

Memory CD8 T cells can provide long-term protection against tumors, which depends on their enhanced proliferative capacity, self-renewal and unique metabolic rewiring to sustain cellular fitness. Specifically, memory CD8 T cells engage oxidative phosphorylation and fatty acid oxidation to fulfill their metabolic demands. In contrast, tumor-infiltrating lymphocytes (TILs) display severe metabolic defects, which may underlie their functional decline.

miR-155 Overexpression in OT-1 CD8 T Cells Improves Anti-Tumor Activity against Low-Affinity Tumor Antigen.

Therapy by adoptive transfer of -expanded tumor-infiltrating or genetically modified T cells may lead to impressive clinical responses. However, there is a need to improve persistence and functionality of the transferred T cells, in particular, to face the highly immunosuppressive environment of solid tumors. Here, we investigate the potential of miR-155, a microRNA known to play an important role in CD8 T cell fitness.

Recombinant fusion proteins for targeting dendritic cell subsets in therapeutic cancer vaccine.

Dendritic cells (DCs) are professional antigen-presenting cells, which are optimal for the priming of a T cell response against pathogens and tumors. Therefore, many efforts are made to develop therapeutic cancer vaccines which preferentially target the antigen to DC subsets. To this aim, we developed two types of recombinant fusion proteins, which favor antigen delivery to pro-inflammatory DCs as well as the crosstalk between specialized subpopulations of DCs.

MicroRNA-155 Expression Is Enhanced by T-cell Receptor Stimulation Strength and Correlates with Improved Tumor Control in Melanoma.

microRNAs are short noncoding RNAs that regulate protein expression posttranscriptionally. We previously showed that miR-155 promotes effector CD8 T-cell responses. However, little is known about the regulation of miR-155 expression.

Combination of Synthetic Long Peptides and XCL1 Fusion Proteins Results in Superior Tumor Control.

Cross-presenting Xcr1CD8α DCs are attractive APCs to target for therapeutic cancer vaccines, as they are able to take up and process antigen from dying tumor cells for their MHCI-restricted presentation to CD8 T cells. To this aim, we developed fusion proteins made of the Xcr1 ligand Xcl1 fused to an OVA synthetic long peptide (SLP) and IgG1 Fc fragment. We demonstrated the specific binding and uptake of the Xcl1 fusion proteins by Xcr1 DCs.

Correction to: CART cells are prone to Fas- and DR5-mediated cell death.

After publication of this article [1], it was noticed that 3 authors were missed from the author list.

Prophylactic vs. Therapeutic Treatment With P2Et Polyphenol-Rich Extract Has Opposite Effects on Tumor Growth.

Polyphenols have tumoricidal effects via anti-proliferative, anti-angiogenic and cytotoxic mechanisms and have recently been demonstrated to modulate the immune response through their anti- or pro- oxidant activity. Nevertheless, it remains controversial whether antioxidant-rich supplements have real beneficial effects on health, especially in complex diseases such as cancer. We previously identified a polyphenol-rich extract obtained from (P2Et) with anti-tumor activity in both breast carcinoma and melanoma.

CART cells are prone to Fas- and DR5-mediated cell death.

Adoptive transfer of T cells transduced with Chimeric Antigen Receptors (CAR) are now FDA-approved for the treatment of B-cell malignancies. Yet, the functionality of the endogenous TCR in CART cells has not been fully assessed. Here, we demonstrate that CART cells progressively upregulate Fas, FasL, DR5 and TRAIL, which result in their programmed cell death, independently of antigen-mediated TCR or CAR activation.

PD-1 Blockade Unleashes Effector Potential of Both High- and Low-Affinity Tumor-Infiltrating T Cells.

Antitumor T cell responses involve CD8 T cells with high affinity for mutated self-antigen and low affinity for nonmutated tumor-associated Ag. Because of the highly individual nature of nonsynonymous somatic mutations in tumors, however, immunotherapy relies often on an effective engagement of low-affinity T cells. In this study, we studied the role of T cell affinity during peripheral priming with single-peptide vaccines and during the effector phase in the tumor.

Alpha-Galactosylceramide/CD1d-Antibody Fusion Proteins Redirect Invariant Natural Killer T Cell Immunity to Solid Tumors and Promote Prolonged Therapeutic Responses.

Major progress in cancer immunotherapies have been obtained by the use of tumor targeting strategies, in particular with the development of bi-functional fusion proteins such as ImmTacs or BiTes, which engage effector T cells for targeted elimination of tumor cells. Given the significance of invariant natural killer T (iNKT) cells in bridging innate and adaptive immunity, we have developed a bi-functional protein composed of the extracellular part of CD1d molecule that was genetically fused to an scFv fragment from high affinity antibodies against HER2 or CEA. Systemic treatments with the CD1d-antitumor fusion proteins loaded with the agonist alpha-galactosylceramide (αGalCer) led to specific iNKT cell activation, resulting in a sustained growth inhibition of established tumors expressing HER2 or CEA, while treatment with the free αGalCer was ineffective.

Very Late Antigen-1 Marks Functional Tumor-Resident CD8 T Cells and Correlates with Survival of Melanoma Patients.

A major limiting factor in the success of immunotherapy is tumor infiltration by CD8 T cells, a process that remains poorly understood. In the present study, we characterized homing receptors expressed by human melanoma-specific CD8 T cells. Our data reveal that P-selectin binding and expression of the retention integrin, very late antigen (VLA)-1, by vaccine-induced T cells correlate with longer patient survival.

Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model.

Recent findings suggest that part of the anti-tumor effects of several chemotherapeutic agents require an intact immune system. This is in part due to the induction of immunogenic cell death. We have identified a gallotannin-rich fraction, obtained from Caesalpinia spinosa (P2Et) as an anti-tumor agent in both breast carcinoma and melanoma.

Mammalian Target of Rapamycin Complex 2 Controls CD8 T Cell Memory Differentiation in a Foxo1-Dependent Manner.

Upon infection, antigen-specific naive CD8 T cells are activated and differentiate into short-lived effector cells (SLECs) and memory precursor cells (MPECs). The underlying signaling pathways remain largely unresolved. We show that Rictor, the core component of mammalian target of rapamycin complex 2 (mTORC2), regulates SLEC and MPEC commitment.