Exosomes in melanoma: A role in tumor progression, metastasis and impaired immune system activity

Exosomes (Exo) are small vesicles produced by melanoma cells and the accessory cells of the tumor microenvironment. They emerge via both classical and direct pathways and actively participate in tumor colonisation of distant tissues. The proteins, nucleic acids, cytokines and growth factors engulfed by Exo are transferred to recipient cells, where they drive numerous functions required for the tumor escape from immune system control and tumor progression. By positively or negatively modulating immune cell properties, Exo provoke immune suppression and, in turn, defective dendritic cell (DC) functions. Together, these effects limit the cytotoxicity of T-cells and expand both T-regulatory and myeloid-derived suppressor populations. They also hinder perforin and granzyme production by natural killer cells. Finally, Exo also control the organotropism of melanoma cells. The distinct phenotypic properties of Exo can be exploited both for diagnostic purposes and in the early identification of melanoma patients likely to respond to immunotherapy. The potential therapeutic application of Exo derived from DCs has been demonstrated in vaccination trials, which showed an increase in anti-melanoma activity with respect to circulating tumor cells. However, additional studies are required before Exo can be effectively used in diagnostic and therapeutic applications in melanoma

CORRIGENDUM to The mechanisms of acute interstitial nephritis in the era of immune checkpoint inhibitors in melanoma

In this article, the authors’ first names and surnames were incorrectly listed in the wrong order. The correct author list is: Marco Tucci, Anna Passarelli, Annalisa Todisco, Francesco Mannavola, Luigia Stefania Stucci, Stella D’Oronzo, Michele Rossini, Marco Taurisano, Loreto Gesualdo and Franco Silvestris

cutaneous metastasis as a primary presentation of a pulmonary enteric adenocarcinoma

Background: Primary pulmonary enteric adenocarcinoma (PEAC) is a rare non-small cell lung cancer subtype sharing morphologic and immunohistochemical features with colorectal adenocarcinoma. Given the frequency of lung metastases in colorectal cancer, the differential diagnosis of PEAC according to routine morphological and immunohistochemical findings may be difficult. Genome sequence by next-generation sequencing has recently introduced new perspectives to better define the diagnosis and tumor sensitivity to treatments, while the rarity of this subtype of cancer still limits the current knowledge of its molecular features and provides no information to address patients to tailored therapies. Methods: We diagnosed a rare case of subcutaneous metastasis as a first symptom of a PEAC. Formalin-fixed paraffin-embedded samples of the primary tumor and subcutaneous metastases were examined by immunohistochemistry, and subsequently by targeted next-generation sequencing analysis. Results: Morphological and immunohistochemical findings suggested a rare case of metastatic pulmonary adenocarcinoma with enteric aspects. Next-generation sequencing analysis performed on both the primary tumor sample and the cutaneous lesion identified two pathogenic variants on CDKN2A and KRAS in both of them. However, the metastasis showed two additional pathogenic mutations located in SMAD4 and FLT3 genes. Conclusions: We describe for the first time an extensive molecular analysis on a rare case of PEAC with an unusual cutaneous metastasis. Our observation suggests that a specific pattern of mutations is harbored in this neoplasm, and that additional molecular studies may provide further information to identify prognostic and hopefully predictive genes of response to treatment

Vitamin D in melanoma: Controversies and potential role in combination with immune check-point inhibitors

The role of vitamin D in melanoma is still controversial. Although several Authors described a correlation between vitamin D deficiency and poor survival in metastatic melanoma patients, clinical trials exploring the effects of vitamin D supplementation in this clinical setting were mostly inconclusive. However, recent evidence suggests that vitamin D exerts both anti-proliferative effects on tumor cells and immune-modulating activities, that have been widely explored in auto-immune disorders. On the one hand, vitamin D has been shown to inhibit T-helper17 lymphocytes, notoriously involved in the pathogenesis of immune-related adverse events (iAEs) which complicate immune-checkpoint inhibitor (ICI) treatment. On the other hand, vitamin D up-regulates PDL-1 expression on both epithelial and immune cells, suggesting a synergic effect in combination with ICIs, for which further investigation is needed

COVID 19: HEALTH, STATISTICAL AND CONSTITUTIONAL ASPECTS

Starting from the assumption that “health is the primary good" and although the humanitarian character of the epidemic remains the most urgent aspect to be treated, unfortunately it is not the only one. As acknowledged by the World Health Organization on 11 March, the COVID-19 epidemic has become a worldwide pandemic. The response to the emergency connected with the spread of the virus, to limit its negative impact on the economic system, must consist in a rapid and targeted intervention. The aim of this paper is to analyse the main aspects of Covid 19 from the point of view of health, constitutional and statistical, highlighting the evolution of the phenomenon and its territorial diffusion, with reference to the spread of the virus in Italy

Cancer treatment-induced bone loss (CTIBL): Pathogenesis and clinical implications.

Osteopenia and osteoporosis are often long-term complications of anti-neoplastic treatments, defined as ‘‘cancer treatment-induced bone loss” (CTIBL). This pathological condition in oncologic patients results in a higher fracture risk than in the general population, and so has a significant negative impact on their quality of life. Hormone treatment is the main actor in this scenario, but not the only one. In fact, chemotherapies, radiotherapy and tyrosine kinase inhibitors may contribute to deregulate bone remodeling via different mechanisms. Thus, the identification of cancer patients at risk for CTIBL is essential for early diagnosis and appropriate intervention, that includes both lifestyle modifications and pharmacological approaches to prevent bone metabolism failure during anti-tumor treatments

Drug therapy of advanced cutaneous squamous cell carcinoma: is there any evidence?

PURPOSE OF REVIEW There are few randomized controlled studies to guide the treatment of advanced cutaneous squamous cell carcinoma. The existing treatments are mostly based on case reports and small case series. Here we review recently available insights concerning the treatment of locally advanced and metastatic squamous cell carcinoma, with a special emphasis on novel targeted therapy and immunotherapy. RECENT FINDINGS Surgery and combination of chemotherapy and radiation therapy have been long considered the gold standard options for advanced squamous cell carcinoma. The detection of clinically relevant driver mutations has opened the door to the use of novel targeted therapies. Recent studies have shown that aggressive cutaneous squamous cell carcinoma is characterized by a very high mutational background. Furthermore, the importance of the defective immunosurveillance in the growth of cutaneous squamous cell carcinoma and the critical role of programed cell death protein 1 and programmed death-ligand 1 interaction in skin tumor development provides a rationale for the use of immune checkpoint inhibitors. SUMMARY Epidermal growth factor receptor inhibitors have shown to have satisfactory antitumor activity with acceptable side-effect profile. However, their place in management of advanced cutaneous squamous cell carcinoma alone or in combination with either radiation therapy and/or chemotherapy needs to be better characterized. The available preliminary findings suggest that immune checkpoint inhibitors represent a potentially valuable alternative in cutaneous aggressive squamous cell carcinoma, promising a further expansion of their indication spectrum. Randomized controlled studies will allow us to better characterize their practical value

The clonal heterogenicity of circulating tumor cells (CTCs) drives their metastatic potential: a new NOD-SCID melanoma model

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