Melanoma Research最新文献

It is estimated that about 1-13% of melanoma patients will develop multiple primary melanomas. Although the occurrence of subsequent tumors has been described during the last few years, the development of simultaneous melanomas has not yet been extensively studied. We reviewed our registries to identify patients with multiple primary melanomas. We studied epidemiological, clinical, and histological characteristics of patients who were diagnosed with simultaneous melanomas and compared them with those of patients who developed non-synchronous multiple primary melanomas. As simultaneous were defined subsequent melanomas that were diagnosed either at the same visit or within a time-period of maximum of 1 month. Between 2000 and 2020, 2500 patients were diagnosed with melanoma at Andreas Syggros Hospital. 86 (3.4%) patients presented multiple primary melanomas and among them, 35 (40.7%) developed simultaneous melanomas. Patients with simultaneous melanomas developed more frequently more than 2 tumors. First tumors of patients with non-synchronous melanomas were significantly thicker than second tumors while those of patients with simultaneous melanomas did not differ significantly. Slight differences in the tumor localization, staging and histologic type were observed between the two groups. However significant differences were ascertained between first and second tumors in both groups. Simultaneous melanomas occupy an important proportion of multiple primary melanomas, affecting a non-negligible number of patients. Slight differences between simultaneous and non-synchronous multiple primary melanomas seem to define a distinct subcategory of multiple primary melanomas.

Most of the studies have reported the downregulation of miR-9 in metastatic melanomas compared to primary tumors. They indicated that miR-9 negatively regulates the epithelial-to-mesenchymal transition (EMT) by inhibiting SNAIL1 expression and consequently promotes CDH1 expression. Since the process of EMT is associated to stem cell features, it could be interesting to study the effect of miR-9 on melanoma cancer stem cells. In the present study, we examined the effects of miR-9 manipulation on the stemness potential of melanoma cells. Our data demonstrated that the overexpression of miR-9 in A375 and NA8 cells significantly inhibits the ability of proliferation, self-renewal, migration, and tumorigenicity of melanoma cells which was concomitant with changes in the level of BRAF , some EMT factors, and stemness genes. Likewise, the reduction of miR-9 levels led to an increase in cell proliferation, colony and sphere formation, and the ability of cell migration and tumorigenicity. In conclusion, our results specified the role of miR-9 as a tumor suppressor miRNA to inhibit many aspects of melanoma stem cells, and therefore, it could be a potential candidate for the suppression of melanoma growth and progression.

Hypoxia has established associations with aggressive tumor phenotypes in many cancers. However, it is not currently understood whether tumor hypoxia levels map to distinct immune infiltrates in cutaneous melanoma, potentially unveiling novel therapeutic targets. To this end, we leveraged a previously identified seven-gene hypoxia signature to grade hypoxia levels of 460 cutaneous melanomas obtained from the Broad Institute GDAC Firehose portal. CIBERSORTx ( https://cibersortx.stanford.edu/ ) was employed to calculate the relative abundance of 22 mature human hematopoietic populations. Clinical outcomes and immune cell associations were assessed by computational means. Results indicated that patients with high-hypoxia tumors reported significantly worse overall survival and correlated with greater Breslow depth, validating the in-silico methodology. High-hypoxia tumors demonstrated increased infiltration of activated and resting dendritic cells, resting mast cells, neutrophils, and resting NK cells, but lower infiltration of gamma-delta T cells. These data suggest that high tumor hypoxia correlates with lower survival probability and distinct population differences of several tumor-infiltrating leukocytes in cutaneous melanomas.

Melanoma diagnosed within 1 year of pregnancy is defined as pregnancy-associated melanoma (PAM). No robust data on how pregnancy influences melanoma nor guidelines for PAM management exist. With IRB approval, female patients with a pathology-confirmed melanoma diagnosis within 1 year of pregnancy treated at our institution from 2000 to 2020 were identified. Controls from the cancer registry were matched 1 : 4 when available on decade of age, year of surgery (±5), and stage. We identified 83 PAM patients with median follow-up of 86 months. Mean age at diagnosis was 31 years. 80% AJCC V8 stage I, 2.4% stage II, 13% stage III, 4.8% stage IV. Mean Breslow thickness was 0.79 mm and 3.6% exhibited ulceration. The mean mitotic rate was 0.76/mm 2 . In terms of PAM management, 98.6% of ESD patients and 86.7% of LSD patients received standard-of-care therapy per NCCN guidelines for their disease stage. No clinically significant delays in treatment were noted. Time to treatment from diagnosis to systemic therapy for LSD patients was an average of 46 days (95% CI: 34-59 days). Comparing the 83 PAM patients to 309 controls matched on age, stage, and year of diagnosis, similar 5-year overall survival (97% vs. 97%, P  = 0.95) or recurrence-free survival (96% vs. 96%, P  = 0.86) was observed. The outcomes of PAM following SOC treatment at a highly specialized center for melanoma care were comparable to non-PAM when matched by clinical-pathologic features. Specialty center care is encouraged for women with PAM.

The objective of this study is to describe survival outcomes in patients with metastatic melanoma in a real-world setting receiving combination and single-agent immunotherapy outside the clinical trial context. We conducted a retrospective single-institution study of patients with metastatic melanoma in a real-world setting. Survival was calculated using log-rank test. Contingency tables were analyzed using Fisher's Exact test. CD8 + T-cell densities were measured using quantitative immunofluorescence and analyzed using Mann-Whitney U test. The median overall survival (OS) for 132 patients was 45.3 months. Brain metastasis did not confer a higher risk of death relative to liver and/or bone disease (39.53 versus 30.00 months, respectively; P  = 0.687). Anti-PD-1 monotherapy was the most common first-line treatment, received by 49.2% of patients. There was no significant difference in OS between patients receiving single-agent anti-PD-1 and combination anti-PD-1 plus CTLA-4 (39.4 months versus undefined; P  = 0.643). Patients treated with combination therapy were more likely to be alive without progression at the last follow-up than those who received monotherapy (70.4% versus 49.2%; P  = 0.0408). Median OS was 21.8 months after initiation of second-line therapy after anti-PD-1 monotherapy. CD8+ T-cell densities were higher in patients who achieved disease control on first-line immunotherapy ( P  = 0.013). In a real-world setting, patients with metastatic melanoma have excellent survival rates, and treatment benefit can be achieved even after progression on first-line therapy. Combination immunotherapy may produce more favorable long-term outcomes in a real-world setting. High pretreatment CD8+ T-cell infiltration correlates with immunotherapy efficacy.

Malignant melanoma, a rare skin cancer in children, primarily affects individuals over 10 years old. Giant congenital nevi, found in about 1% of newborns, increases the risk. However, the development of melanoma from a pre-existing giant congenital nevus diagnosed during the neonatal period is exceptionally rare. We present a case of congenital melanoma in a newborn, where nodules grew on an existing nevus on the baby's back. Literature on managing such cases was reviewed. This case highlights the importance of considering malignant transformation in congenital nevi and the challenges in their management. Due to limited reported cases over 80 years, conclusive findings on survival and treatment options are difficult to provide. Clinicians should report outcomes to develop a management algorithm for neonatal melanoma. Further studies are needed to enhance understanding of causes and treatment for patients with congenital giant hairy nevi and associated melanoma.

The intricate pathways of the sympathetic nervous system hold an inherently protective role in the setting of acute stress. This is achieved through dynamic immunomodulatory and neurobiological networks. However, excessive and chronic exposure to these stress-induced stimuli appears to cause physiologic dysfunction through several mechanisms that may impair psychosocial, neurologic, and immunologic health. Numerous preclinical observations have identified the beta-2 adrenergic receptor (β2-AR) subtype to possess the strongest impact on immune dysfunction in the setting of chronic stressful stimuli. This prolonged expression of β2-ARs appears to suppress immune surveillance and promote tumorigenesis within multiple cancer types. This occurs through several pathways, including (1) decreasing the frequency and function of CD8 + T-cells infiltrating the tumor microenvironment (TME) via inhibition of metabolic reprogramming during T cell activation, and (2) establishing an immunosuppressive profile within the TME including promotion of an exhausted T cell phenotype while simultaneously enhancing local and paracrine metastatic potential. The use of nonselective β-AR antagonists appears to reverse many chronic stress-induced tumorigenic pathways and may also provide an additive therapeutic benefit for various immune checkpoint modulating agents including commonly utilized immune checkpoint inhibitors. Here we review the translational and clinical observations highlighting the foundational hypotheses that chronic stress-induced β-AR signaling promotes a pro-tumoral immunophenotype and that blockade of these pathways may augment the therapeutic response of immune checkpoint inhibition within the scope of melanoma.