PD-L1 in Melanoma and Extracellular Vesicles Promotes Local and Regional Immune Suppression through M2-like Macrophage Polarization.

Tumor-associated macrophages (TAMs) play dual roles in tumor progression. TAMs are known to induce programmed death ligand-1 (PD-L1) expression in cancer cells. However, the regulatory effects of PD-L1 in melanoma cells on TAM phenotypical switching remain underexplored.

Association between alopecia areata, anxiety, and depression: Insights from a bidirectional two-sample Mendelian randomization study.

Background: As research progresses, there has been growing interest in the association between Alopecia areata (AA) and anxiety, as well as depression. However, there have been limited reports on the genetic variation level of AA in relation to mental disorders.

Method: We performed large-scale Two sample Mendelian randomization (MR) analyses to examine whether there is a association between AA with anxiety and depression.

Age at Natural Menopause, Reproductive Lifespan, and the Risk of Late-Onset Psoriasis and Psoriatic Arthritis in Women: A Prospective Cohort Study.

Although a peak incidence of psoriasis in women aged around 60 years has been observed, the link between reproductive lifespan and late-onset psoriatic diseases is underexplored. This study aims to elucidate the association between reproductive lifespan and the risk of late-onset psoriasis and psoriatic arthritis (PsA). Utilizing the UK Biobank data, we conducted a prospective cohort study in postmenopausal women without baseline psoriatic diseases.

Investigating the gut microbiota's influence on psoriasis and psoriatic arthritis risk: a Mendelian randomization analysis.

Background: Numerous investigations have revealed the interplay between gut microbiota (GM) and psoriasis (Ps) and psoriatic arthritis (PsA). However, the causal relationship between them remains unknown.

Methods: We curated a collection of genetic variants ( < 1 × 10) associated with GM ( = 18 340) derived from the MiBioGen study.

Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer.

Background: Some retrospective studies reported that psoriasis (PsO) and psoriatic arthritis (PsA) may have been associated with an elevated risk of skin cancer. The causal associations among them remain unclear.

Objectives: To evaluate the causal association of among both PsO and PsA, and skin cancer.

TRAF6 regulates autophagy and apoptosis of melanoma cells through c-Jun/ATG16L2 signaling pathway.

Autophagy and apoptosis are essential processes that participate in cell death and maintain cellular homeostasis. Dysregulation of these biological processes results in the development of diseases, including cancers. Therefore, targeting the interaction between apoptosis and autophagy offers a potential strategy for cancer therapy.

NETO2 promotes melanoma progression via activation of the Ca/CaMKII signaling pathway.

Melanoma is the most aggressive cutaneous tumor. Neuropilin and tolloid-like 2 (NETO2) is closely related to tumorigenesis. However, the functional significance of NETO2 in melanoma progression remains unclear.

CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway.

Background: Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear.

Methods: Epidermal CD147-overexpression or knockout (Epi or Epi) transgenic mouse models were generated for in vivo study.

Preclinical platforms to study therapeutic efficacy of human γδ T cells.

Background: Gamma delta (γδ) T lymphocytes are promising candidate for adoptive T cell therapy, however, their treatment efficacy is not satisfactory. Vδ2 T cells are unique to primates and few suitable models are available to assay their anti-tumour function.

Methods: We tested human γδ T cell activation, tumour infiltration, and tumour-killing in four three-dimensional (3D) models, including unicellular, bicellular and multicellular melanoma spheroids, and patient-derived melanoma organoids.

Costimulation of γδTCR and TLR7/8 promotes Vδ2 T-cell antitumor activity by modulating mTOR pathway and APC function.

Background: Gamma delta (γδ) T cells are attractive effector cells for cancer immunotherapy. Vδ2 T cells expanded by zoledronic acid (ZOL) are the most commonly used γδ T cells for adoptive cell therapy. However, adoptive transfer of the expanded Vδ2 T cells has limited clinical efficacy.

Targeting regulatory T cells for immunotherapy in melanoma.

Regulatory T cells (Tregs) are essential in the maintenance of immunity, and they are also a key to immune suppressive microenvironment in solid tumors. Many studies have revealed the biology of Tregs in various human pathologies. Here we review recent understandings of the immunophenotypes and suppressive functions of Tregs in melanoma, including Treg recruitment and expansion in a tumor.

Small extracellular vesicles-based cell-free strategies for therapy.

Small extracellular vesicles (sEVs) are extracellular nanovesicles that contain bioactive proteins, lipids, RNA, and DNA. A variety of biological process is regulated with sEVs. sEVs are an intercellular messenger regulating recipient cell function and play a role in disease initiation and progression.

The plasma exosomal miR-1180-3p serves as a novel potential diagnostic marker for cutaneous melanoma.

Background: Exosomes are a promising tool in disease detection because they are noninvasive, cost-effective, sensitive and stable in body fluids. MicroRNAs (miRNAs) are the main exosomal component and participate in tumor development. However, the exosomal miRNA profile among Asian melanoma patients remains unclear.

Dichotomous and stable gamma delta T-cell number and function in healthy individuals.

Background: Gamma-delta (γδ) T lymphocytes are primed to potently respond to pathogens and transformed cells by recognizing a broad range of antigens. However, adoptive immunotherapy with γδT cells has exhibited mixed treatment responses. Better understanding of γδT cell biology and stratifying healthy donors for allogeneic adoptive therapy is clinically needed to fully realize the therapeutic potential of γδT cells.

Inhibition of xCT suppresses the efficacy of anti-PD-1/L1 melanoma treatment through exosomal PD-L1-induced macrophage M2 polarization.

Tumor cells increase glutamate release through the cystine/glutamate transporter cystine-glutamate exchange (xCT) to balance oxidative homeostasis in tumor cells and promote tumor progression. Although clinical studies have shown the potential of targeting programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling in melanoma, response rates are low. However, it remains unclear how glutamate metabolism affects anti-PD-1/PD-L1 treatment efficacy in melanoma.

Unemployment and Health-Related Quality of Life in Melanoma Patients During the COVID-19 Pandemic.

The outbreak of coronavirus disease-2019 (COVID-19) ineluctably caused social distancing and unemployment, which may bring additional health risks for patients with cancer. To investigate the association of the pandemic-related impacts with the health-related quality of life (HRQoL) among patients with melanoma during the COVID-19 pandemic, we conducted a cross-sectional study among Chinese patients with melanoma. A self-administered online questionnaire was distributed to melanoma patients through social media.

Pyruvate kinase M2 (PKM2) in cancer and cancer therapeutics.

Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme of glycolysis, is a critical regulator in tumor metabolism. PKM2 has been demonstrated to overexpressed in various cancers and promoted proliferation and metastasis of tumor cells. The errant expression of PKM2 has inspired people to investigate the function of PKM2 and the therapeutic potential in cancer.

Association of Socioeconomic Changes due to the COVID-19 Pandemic With Health Outcomes in Patients With Skin Diseases: Cross-Sectional Survey Study.

Background: The outbreak of COVID-19 has profoundly influenced people's lifestyles; these impacts have varied across subgroups of people. The pandemic-related impacts on the health outcomes of people with dermatological conditions are unknown.

Objective: The aim of this paper was to study the association of COVID-19 pandemic-related impacts with health-related quality of life in patients with skin diseases.

The phosphorylation of CD147 by Fyn plays a critical role for melanoma cells growth and metastasis.

CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a transmembrane glycoprotein that is highly expressed in tumor cells, particularly melanoma cells, and plays critical roles in tumor cell metastasis through the regulation of matrix metalloprotease (MMP) expression. In this study, we identified Fyn as a novel interacting protein of CD147. Fyn is a member of the Src family of nonreceptor tyrosine kinases that regulates diverse physiological processes, such as T lymphocyte differentiation, through the TCR signaling pathway.

TRAF6 Activates Fibroblasts to Cancer-Associated Fibroblasts through FGF19 in Tumor Microenvironment to Benefit the Malignant Phenotype of Melanoma Cells.

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment and mediate tumor progression in various cancers. A previous study demonstrated that TRAF6 promotes the malignant phenotype of melanoma cells. However, the role of TRAF6 in melanoma CAFs remains unclear.

Autophagy in Skin Diseases.

Autophagy, or self-eating, is an evolutionarily conserved process in which cytosol and organelles are sequestered within double-membrane vesicles that deliver the contents to the lysosome/vacuole for the degradation and recycling of cytoplasmic components in eukaryotes. It is well recognized that autophagy plays an important role in maintaining cellular homeostasis under physiological and pathophysiological con-ditions and the upregulation of autophagy may serve as an adaptive process to provide nutrients and energy when under stresses. Recently, studies have illustrated that autophagy is intricately related to skin diseases.