A comparison of myeloid-derived suppressor cell populations in patients with ulcerated vs non-ulcerated melanoma receiving immune checkpoint blockade.

Myeloid-derived suppressor cells (MDSCs) are expanded in cancer patients, have an intrinsic immunosuppressive function, and thus may play a role in resistance to immunotherapy. Ulceration of the melanoma primary is associated with more aggressive disease and is an independent prognostic factor for melanoma-specific survival. However, the underlying factors contributing to this more aggressive phenotype are not completely understood.

Targeting Myeloid-Derived Suppressor Cells via Dual-Antibody Fluorescent Nanodiamond Conjugate.

Fluorescent nanodiamonds (FNDs) are carbon-based nanomaterials that emit bright, photostable fluorescence and exhibit a modifiable surface chemistry. Myeloid-derived suppressor cells (MDSCs) are an immunosuppressive cell population known to expand in cancer patients and contribute to worse patient outcomes. To target MDSC, glycidol-coated FND were conjugated with antibodies against the murine MDSC markers, CD11b and GR1 (dual-Ab FND).

BTK inhibition potentiates anti-PD-L1 treatment in murine melanoma: potential role for MDSC modulation in immunotherapy.

Myeloid-derived suppressor cells (MDSC) have been linked to loss of immune effector cell function through a variety of mechanisms such as the generation of reactive oxygen and nitrogen species and the production of inhibitory cytokines. Our group has shown that signaling through Bruton's tyrosine kinase (BTK) is important for MDSC function. Ibrutinib is an orally administered targeted agent that inhibits BTK activation and is currently used for the treatment of B cell malignancies.

Expression of microRNAs and their target genes in melanomas originating from gynecologic sites.

Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that MOGS would display unique miR and mRNA expression profiles.

Expression Patterns of microRNAs and Associated Target Genes in Ulcerated Primary Cutaneous Melanoma.

Ulcerated cutaneous melanoma carries a poor prognosis, and the underlying biology driving its aggressive behavior is largely unexplored. MicroRNAs (miRs) are small, noncoding RNAs that inhibit the expression of specific genes and exhibit dysregulated expression patterns in cancer. We hypothesized that a unique miR profile exists in ulcerated relative to nonulcerated melanoma and that miR expression inversely correlates with target genes of biologic importance.

Ulcerated Cutaneous Melanoma: A Review of the Clinical, Histologic, and Molecular Features Associated with a Clinically Aggressive Histologic Phenotype.

The presence of ulceration in melanoma is associated with poor clinical outcomes and is the third most powerful predictor of survival in the AJCC Melanoma Staging System after tumor thickness and mitotic activity. The aggressive biological behavior associated with ulceration has been hypothesized to be the result of an intrinsic biological attribute that favors dissemination and presents locally with the loss of epidermal integrity. Among the features of ulcerated melanoma, many show promise as potential prognostic tools, markers of differential immunogenicity and indicators of oncogenic drivers of invasion and metastasis.

CCN2 participates in overload-induced skeletal muscle hypertrophy.

The regulation of skeletal muscle growth following pro-hypertrophic stimuli requires a coordinated response by different cell types that leads to extracellular matrix (ECM) remodeling and increases in muscle cross-sectional area. Indeed, matricellular proteins serve a key role as communication vehicles that facilitate the propagation of signaling stimuli required for muscle adaptation to environmental challenges. We found that the matricellular protein cellular communication network factor 2 (CCN2), also known as connective tissue growth factor (CTGF), is induced during a time course of overload-driven skeletal muscle hypertrophy in mice.