Extracorporeal photochemotherapy (ECP) is a cancer immunotherapy for cutaneous T-cell lymphoma (CTCL) operative in more than 350 centers worldwide. Although its efficacy and favorable safety profile have driven its widespread use, elucidation of its underlying mechanism has been difficult. In this study, we identify the principal contributors to the anticancer immunotherapeutic effects of ECP, with the goal of enhancing potency and broadening applicability to additional malignancies. First, we scaled down the clinical ECP leukocyte-processing device to mouse size. Second, we used that miniaturized device to produce a cellular vaccine that regularly initiated therapeutic antimelanoma immunity. Third, we individually subtracted key factors from either the immunizing inoculum or the treated animal to ascertain their contribution to the antimelanoma response. Platelet-signaled monocyte-to-dendritic cell (DC) differentiation followed by sorting/processing/presentation of tumor antigens derived from internalized apoptotic tumor cells were absolute requirements. As in clinical ECP, immunogenic cell death of tumor cells was finely titrated by DNA cross-linkage mediated by photoactivated 8-methoxypsoralen (8-MOPA). ECP-induced tumor-loaded DC were effective immunotherapeutic agents only if they were spared exposure to 8-MOPA, indicating that healthy DC are required for ECP. Infusion of responder T cells into naïve tumor-challenged mice established the protective role of stimulated T-cell antitumor immunity. Collectively, these results reveal that selective antitumor effects of ECP are initiated by tumor antigen-loaded, ECP-induced DC, which promote potent collaboration between CD4 and CD8 tumor-specific T cells. These mechanistic insights suggest potential therapeutic applicability of ECP to solid tumors in addition to CTCL. These findings identify principal cellular contributors to the anticancer immunotherapeutic impact of ECP and suggest this treatment may be applicable to a broad spectrum of immunogenic malignancies. .

Psoriasis is a chronic inflammatory disease affecting up to 3% of the general population. The prevalence of nail involvement in psoriasis patients varies between 15% and 79%. While the nails represent a small portion of the body surface area, psoriasis in these areas can have a disproportionate influence on a patient’s physical and psychosocial activities. Differential diagnosis between an onychomycosis and a psoriatic nail could be challenging; nevertheless, coexistence of onychomycosis and nail psoriasis also occurs and both are common disorders in the general population. Nail psoriasis can be difficult to treat. Treatment of nail psoriasis should consider the body surface area of skin disease, psoriatic arthritis, severity of nail disease, and the impairment in the quality of life. All patients should be tested for onychomycosis before starting a therapy. This recommendation is underlined by the fact that nail psoriasis is mostly treated by immunosuppressive drugs, like steroids, methotrexate, or biologics, which may aggravate mycotic nail infections. Conventional systemic therapy, such as use of steroids, cyclosporine, methotrexate, and retinoid in the long term, can cause organ toxicities. Currently, use of apremilast and tofacitinib favors an early healing of nail psoriasis because they act directly on the pathogenic targets, distressing the inflammatory signals associated with the initiation and maintenance of the disease activity, and as with several conventional synthetic disease modifying antirheumatic drugs, they are characterized by the convenience of oral administration. The number of treatment options has increased considerably in recent years; however, given the heterogeneity of the disease, the therapy should be personalized to individual cases.

ObjectiveTo identify trends in patient presentation and outcomes data that may guide the development of clinical algorithms on Merkel Cell Carcinoma (MCC).MethodsWe performed a retrospective cohort study searching in the National Cancer Institute's SEER registry for documented MCC cases from 1986-2013. No exclusion criteria were applied. We hereby identified 7,831 original MCC entries. Demographics, staging, and socioeconomic characteristics were identified and treatment modality likelihoods and survival data were calculated via logistic regression and Kaplan-Meier statistical modeling.ResultsConcerning tumor localization, 44.5% (n= 3,485) were located on the head and neck, and 47.8% were located on the trunk and extremities (n= 3,742). Male and younger patients are more likely to receive radiation than surgery with no differences seen among patient race. Caucasians and “Other” races both showed higher overall survival than African American patients. States with higher median household income levels demonstrated survival advantage. Income quartiles yielded no differences in surgical or radiotherapy interventions. Moreover, patients who forego radiotherapy had a poorer overall survival.LimitationsGeneralizability of SEER data, potential intrinsic coding inconsistencies, and limited information on patient comorbidities, sentinel lymph node and surgical margin status are major limitations. There is no information regarding medical intervention such as systemic chemotherapy or immunotherapy. Recoding efforts are inconclusive regarding variables such as tumor infiltrating lymphocytes, mutations, or immunosuppression status, which are well-documented for other cancers within the database.ConclusionMCC lesions of the head and neck region, lower income quartiles, and African American race are associated with higher mortality. MCC patients have a median household income that is significantly higher than national values with no significant difference in subsequent treatment modalities (surgery or radiotherapy) based on socioeconomic markers. A lack of radiotherapy is associated with higher mortality.

This proof-of-concept study supports the efficacy of 5% ALA thermosetting gel red-light PDT in inflammatory acne of the face with a relevant clinical improvement of inflammatory lesions with a very good tolerability profile. Clinical improvement was maintained in the medium term (Trial Registration Number: ISRCTN66066651).

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Despite improvements in survival in metastatic melanoma with combined BRAF and mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor treatment, the overwhelming majority of patients eventually acquire resistance to both agents. Consequently, new targets for therapy in resistant tumors are currently being evaluated. Previous studies have identified p90 subfamily of ribosomal S6 kinase (p90RSK) family kinases as key factors for growth and proliferation, as well as protein synthesis via assembly of the 7-methyl-guanosine triphosphate cap-dependent translation complex. We sought to evaluate inhibitors of p90RSK family members: BI-D1870 and BRD7389, for their ability to inhibit both proliferation and protein synthesis in patient-derived melanoma cell lines with acquired resistance to combined treatment with the BRAF inhibitor vemurafenib and the mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor selumetinib. We found that the RSK inhibitors blocked cell proliferation and protein synthesis in multiple dual-resistant melanoma lines. In addition, single agent RSK inhibitor treatment was effective in drug-naïve lines, two of which are innately vemurafenib resistant. We also used Reverse Phase Protein Array screening to identify differential protein expression that correlates with BI-D1870 sensitivity, and identified prognostic biomarkers for survival in human melanoma patients. These findings establish p90RSK inhibition as a therapeutic strategy in treatment-resistant melanoma and provide insight into the mechanism of action.

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