Circulating interleukin-8 and osteopontin are promising biomarkers of clinical outcomes in advanced melanoma patients treated with targeted therapy.

Background: Circulating cytokines can represent non-invasive biomarkers to improve prediction of clinical outcomes of cancer patients. Here, plasma levels of IL-8, CCL4, osteopontin, LIF and BDNF were determined at baseline (T0), after 2 months of therapy (T2) and, when feasible, at progression (TP), in 70 melanoma patients treated with BRAF and MEK inhibitors. The association of baseline cytokine levels with clinical response, progression-free survival (PFS) and overall survival (OS) was evaluated.

Tumoral inflammatory infiltrate does not predict metastases in thin primary cutaneous melanomas.

Background: In cutaneous melanomas in general, tumor inflammatory infiltrate (TII) can protect against distant metastases, but there is no consensus when only thin primary cutaneous melanomas (TPCM) are considered.

Objective: To investigate the presence of TII in TPCM and the relationship between TII and the occurrence of metastases.

Methods: Case-control study including 50 patients with TPCM, 22 metastatic (MC group) and 28 non-metastatic (NMC group).

Targeting of PDGF-C/NRP-1 autocrine loop as a new strategy for counteracting the invasiveness of melanoma resistant to braf inhibitors.

Melanoma resistance to BRAF inhibitors (BRAFi) is often accompanied by a switch from a proliferative to an invasive phenotype. Therefore, the identification of signaling molecules involved in the development of metastatic properties by resistant melanoma cells is of primary importance. We have previously demonstrated that activation of neuropilin-1 (NRP-1) by platelet-derived growth factor (PDGF)-C confers melanoma cells with an invasive behavior similar to that of BRAFi resistant tumors.

Pituitary Enlargement and Hypopituitarism in Patients Treated with Immune Checkpoint Inhibitors: Two Sides of the Same Coin?

Background: Immune checkpoint inhibitor hypophysitis (IIHs) is an emerging problem in cancer patients treated with immune checkpoint inhibitors (ICIs). We aimed to describe the clinical and molecular features of a multicenter series of IIHs.

Methods: Demographic and clinical features were retrospectively collected for all cases.

Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy.

Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi.

[Management of small cell lung cancer patient in the regions of Lazio, Umbria and Sardinia.].

Small cell lung cancer (SCLC) is an aggressive disease, difficult to treat. There have been no significant therapeutic advances over platinum and etoposide chemotherapy in the last 20 years until the introduction of immunotherapy. In 2020 atezolizumab, an immune checkpoint inhibitor against PD-L1 was approved in Italy in combination with carboplatin and etoposide for the first-line treatment of patients with extensive stage disease (ES-SCLC), becoming the new standard treatment.

Investigating Serum and Tissue Expression Identified a Cytokine/Chemokine Signature as a Highly Effective Melanoma Marker.

The identification of reliable and quantitative melanoma biomarkers may help an early diagnosis and may directly affect melanoma mortality and morbidity. The aim of the present study was to identify effective biomarkers by investigating the expression of 27 cytokines/chemokines in melanoma compared to healthy controls, both in serum and in tissue samples. Serum samples were from 232 patients recruited at the IDI-IRCCS hospital.

Reduction of T Lymphoma Cells and Immunological Invigoration in a Patient Concurrently Affected by Melanoma and Sezary Syndrome Treated With Nivolumab.

Despite the recent availability of several new drugs in hemato-oncology, T-cell lymphomas are still incurable and PD-1 blockade could represent a therapeutic chance for selected patients affected by these malignancies, although further studies are required to understand the biological effects of anti-PD-1 mAbs on neoplastic T-cells and to identify biomarkers for predicting and/or monitoring patients' response to therapy. Sezary Syndrome (SS) represents a rare and aggressive variant of cutaneous T cell lymphoma (CTCL) with a life expectancy of less than 5 years, characterized by the co-presence of neoplastic lymphocytes mainly in the blood, lymph nodes and skin. In this study we analyzed longitudinal blood samples and lesional skin biopsies of a patient concurrently affected by SS and melanoma who underwent 22 nivolumab administrations.

Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: the multicenter FAMI-L1 study.

: We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy. : This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative.

Anti-PD1 antibodies in patients aged ≥ 75 years with metastatic melanoma: A retrospective multicentre study.

Background: Advanced age is associated with comorbidities and immune system impairment, which may influence the efficacy and tolerability of immune checkpoint inhibitors. There is evidence that anti-PD1 antibodies in advanced melanoma are equally effective in patients >65 years. However, data on patients >75 years are lacking as co-morbidities and logistics often exclude them from clinical trials.

Dabrafenib plus trametinib is effective in the treatment of BRAF V600-mutated metastatic melanoma patients: analysis of patients from the dabrafenib plus trametinib Named Patient Program (DESCRIBE II).

In clinical trials, dabrafenib plus trametinib improved overall survival (OS) compared with single-agent BRAF inhibitors (BRAFi) in patients with BRAF V600-mutant unresectable or metastatic melanoma. We investigated dabrafenib plus trametinib therapy in a compassionate-use setting [Named Patient Program (NPP); DESCRIBE II]. A retrospective chart review of patients with BRAF V600-mutated unresectable stage III/IV melanoma receiving dabrafenib plus trametinib as compassionate use was conducted.

miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A.

Background: Development of resistance to inhibitors of BRAF (BRAFi) and MEK (MEKi) remains a great challenge for targeted therapy in patients with BRAF-mutant melanoma. Here, we explored the role of miRNAs in melanoma acquired resistance to BRAFi.

Methods: miRNA expression in two BRAF-mutant melanoma cell lines and their dabrafenib-resistant sublines was determined using Affymetrix GeneChip® miRNA 3.

Stereotactic radiosurgery combined with nivolumab or Ipilimumab for patients with melanoma brain metastases: evaluation of brain control and toxicity.

Purpose: To investigate the efficacy and safety of concurrent stereotactic radiosurgery (SRS) and ipilimumab or nivolumab in patients with untreated melanoma brain metastases.

Patients And Methods: Eighty consecutive patients with 326 melanoma brain metastases receiving SRS in combination with ipilimumab or nivolumab were identified from an institutional database and retrospectively evaluated. Patients started systemic treatment with intravenous nivolumab or ipilimumab within one week of receiving SRS.

A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable.

Background: Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients.

Patients And Methods: We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (< 25).

Clinical Outcomes of Patients with Advanced Cancer and Pre-Existing Autoimmune Diseases Treated with Anti-Programmed Death-1 Immunotherapy: A Real-World Transverse Study.

Background: Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors.

Materials And Methods: Consecutive patients with advanced cancer, treated with anti-programmed death-1 (PD-1) agents, were evaluated according to the presence of pre-existing AIDs. The incidence of immune-related adverse events (irAEs) and clinical outcomes were compared among subgroups.

Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study.

CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and improves overall survival (OS) in a minority of metastatic melanoma (MM) patients. We investigated the role of soluble CTLA-4 (sCTLA-4) as a possible biomarker for identifying this subset of patients. sCTLA-4 levels were analyzed at baseline in sera from 113 IPI-treated MM patients by ELISA, and the median value (200 pg/ml) was used to create two equally sized subgroups.

Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is a novel marker for patients with BRAF-mutated metastatic melanoma.

Metastatic melanoma carrying BRAF mutations represent a still unmet medical need as success of BRAF inhibitors is limited by development of resistance. Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme in NAD biosynthesis. An extracellular form (eNAMPT) possesses cytokine-like functions and is up-regulated in inflammatory disorders, including cancer.

Corrigendum: Association of CTLA-4 Gene Variants with Response to Therapy and Long-term Survival in Metastatic Melanoma Patients Treated with Ipilimumab: An Italian Melanoma Intergroup Study.

[This corrects the article on p. 386 in vol. 8, PMID: 28446908.

Targeting the oncogene impairs proliferation and invasiveness of melanoma cells sensitive or with acquired resistance to the BRAF inhibitor dabrafenib.

The () is implicated in tumor growth, metastasis and drug resistance. Here, we investigated the involvement of in melanoma cell proliferation, invasiveness and response to the BRAF inhibitor (BRAFi) dabrafenib. We also preliminary assessed the potential value of circulating PTTG1 protein to monitor melanoma patient response to BRAFi or to dabrafenib plus trametinib.

Baseline relative eosinophil count as a predictive biomarker for ipilimumab treatment in advanced melanoma.

As diverse therapeutic options are now available for advanced melanoma patients, predictive markers that may assist treatment decision are needed. A model based on baseline serum lactate dehydrogenase (LDH), peripheral blood relative lymphocyte counts (RLC) and eosinophil counts (REC) and pattern of distant metastasis, has been recently proposed for pembrolizumab-treated patients. Here, we applied this model to advanced melanoma patients receiving chemotherapy ( 116) or anti-CTLA-4 therapy ( 128).

Association of CTLA-4 Gene Variants with Response to Therapy and Long-term Survival in Metastatic Melanoma Patients Treated with Ipilimumab: An Italian Melanoma Intergroup Study.

Ipilimumab (IPI) blocks CTLA-4 immune checkpoint resulting in T cell activation and enhanced antitumor immunity. IPI improves overall survival (OS) in 22% of patients with metastatic melanoma (MM). We investigated the association of CTLA-4 single nucleotide variants (SNVs) with best overall response (BOR) to IPI and OS in a cohort of 173 MM patients.

Targeting the PI3K/AKT/mTOR pathway overcomes the stimulating effect of dabrafenib on the invasive behavior of melanoma cells with acquired resistance to the BRAF inhibitor.

BRAF inhibitors (BRAFi) have proven clinical benefits in patients with BRAF-mutant melanoma. However, acquired resistance eventually arises. The effects of BRAFi on melanoma cell proliferation and survival have been extensively studied, and several mechanisms involved in acquired resistance to the growth suppressive activity of these drugs have been identified.

Placenta growth factor and neuropilin-1 collaborate in promoting melanoma aggressiveness.

The placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family, which shares with VEGF-A the tyrosine kinase receptor VEGFR-1 and the co-receptor neuropilin-1 (NRP-1). In melanoma models, PlGF enhances tumour growth and neovessel formation, whereas NRP-1 promotes the metastatic process. Increased secretion of PlGF and expression of NRP-1 have also been involved in intrinsic or acquired resistance to anti‑angiogenic therapies.