Publications by authors named "Margaret Ottaviano"

: Chimeric antigen receptor T-cell (CAR-T) therapy is a novel form of adoptive cellular immunotherapy that involves modifying autologous T cells to recognize and target tumor-associated antigens (TAAs) on malignant cells, independent of major histocompatibility complex (MHC) restriction. Although CAR-T therapy has shown remarkable success in treating hematologic malignancies, its efficacy in solid tumors remains limited, largely due to the lack of tumor-specific antigens and the complexity of the tumor microenvironment. This review aims to explore the rationale for continuing the development of adoptive cellular therapies in head and neck cancer (HNC), offering insights into the diagnostic and therapeutic challenges associated with this heterogeneous group of malignancies.

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Objectives: To identify predictive gene-expression signatures for immune-related adverse events (irAEs) in patients with melanoma treated with anti-PD-1 inhibitors, in the adjuvant therapy (AT) and first-line therapy (FLT).

Methods: This retrospective study analyzed baseline whole-blood gene expression profile from 161 patients with resected stage III or unresectable stage III-IV melanoma treated with anti-PD-1 inhibitors. RNA was extracted from baseline peripheral blood samples and profiled using the NanoString nCounter PanCancer IO 360 panel.

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Gastric cancer (GC), one of the tumours with the highest mortality worldwide, is not a homogeneous disease, showing different features according to location, macroscopic aspect, histotype and molecular alterations. Adenocarcinoma is the most frequent epithelial GC (95%), the remaining 5% comprising rare epithelial tumours with their peculiarities, behaviour and incidence <6 cases/100,000/year. Due to the low number of cases, many aspects must be elucidated in this context.

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Malignant melanoma represents the fifth most common cancer in the world and its incidence is rising. Novel therapies targeting receptor tyrosine kinases, kinases and immune checkpoints have been employed with a significant improvement of the overall survival and long-term disease containment. Nevertheless, the disease often progresses and becomes resistant to the therapies.

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Testicular germ cell tumors (TGCTs), the most common malignancies affecting young men, are characterized by high sensitivity to cisplatin-based chemotherapy, which leads to high cure rates even in metastatic disease. However, approximately 30% of patients with metastatic TGCTs relapse after first-line treatment and those who can be defined as platinum-refractory patients face a very dismal prognosis with only limited chemotherapy-based treatment options and an overall survival of few months. Hence, to understand the mechanisms underlying cisplatin resistance is crucial for developing new treatment strategies.

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Immune checkpoint inhibitors (ICI) can achieve durable responses in patients with advanced melanoma, and results from clinical trials suggest cure may be possible for a subset of patients. Despite clinical trial data, little is known about the risk, character, and clinical outcome of late recurrences after ICI. This study aimed to explore the disease outcomes and survival in a cohort of patients with long-term responses to ICI.

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We previously demonstrated that patients with metastatic unresectable stage IIIb-IV melanoma receiving cetirizine (a second-generation H1 antagonist antihistamine) premedication with immunotherapy had better outcomes than those not receiving cetirizine. In this retrospective study, we searched for a gene signature potentially predictive of the response to the addition of cetirizine to checkpoint inhibition (nivolumab or pembrolizumab with or without previous ipilimumab). Transcriptomic analysis showed that inducible T cell costimulator ligand (ICOSLG) expression directly correlated with the disease control rate (DCR) when detected with a loading value > 0.

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Thymic epithelial tumors are rare malignancies with an incidence of 1.7 cases per million people per year. They pose significant management challenges due to their association with autoimmune disorders.

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Article Synopsis
  • Thymic epithelial tumors (TETs) are rare tumors often linked to immune issues, like Good's syndrome (GS), which increases mortality risk from infections.
  • The study reviewed COVID-19 incidence and severity among TET patients from March 2020 to April 2023, noting that about 66% of participants contracted COVID-19, regardless of GS presence.
  • Results showed a significant correlation between GS and increased COVID-19 severity, with 45% of GS patients experiencing higher severity scores compared to just 7.7% in patients without GS.
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Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is lacking. A retrospective study was performed to evaluate the survival of patients with cutaneous squamous cell carcinoma (CSCC) who discontinued cemiplimab due to different causes and without progression. Among 95 patients with CSCC who received cemiplimab, 22 (23%) patients discontinued immunotherapy due to causes other than progression, such as comorbidities, toxicity, complete response or lack of compliance (group that discontinued before censoring [DBC]), then 73 patients had standard treatment scheduled (STS).

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  • Thymic epithelial tumors (TETs) are rare cancers often linked to autoimmune disorders and severe immunodeficiency, which complicates responses to COVID-19 vaccines.
  • A study was conducted to assess immune responses to the SARS-Cov-2 mRNA vaccine in TET patients, focusing on humoral and cellular responses and vaccination safety over a full cycle including a booster.
  • The results showed significant immune responses post-vaccination, with a correlation between baseline lymphocyte levels and vaccine effectiveness, and most patients did not experience severe COVID-19 even when infected during the study period.
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  • * High baseline NLR correlates with poorer patient prognosis and specific gene signatures associated with inflammation and tumor growth, while low NLR indicates immune activation.
  • * The findings suggest that an increase in NLR relates to a rise in immunosuppressive neutrophils, contributing to a negative impact on treatment outcomes for patients.
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  • Thymic epithelial tumors (TETs) are rare cancers that affect the immune system, and this study investigates how patients with TET respond to the SARS-CoV-2 mRNA vaccine after two doses.
  • The study involved 39 patients, analyzing their antibody levels before and after vaccination, revealing that all had negative antibody levels before vaccination, with differences in seroconversion based on their disease status.
  • Results indicated that patients with evidence of disease (ED) had a significantly lower chance of generating an immune response compared to those with no evidence of disease, highlighting the impact of their existing health conditions on vaccine effectiveness.
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  • - Sarcomas of the thoracic cavity, particularly Ewing Sarcoma (ES), are rare and primarily impact children and young adults, with ES being the second most common thoracic sarcoma after chondrosarcoma.
  • - Despite its rarity in the thoracic cavity, ES behaves similarly to cases outside this area, requiring multi-faceted treatment approaches including surgery, radiotherapy, and systemic therapy, though the long-term prognosis remains poor.
  • - There is a need for further research into the molecular mechanisms behind ES to develop new therapies, as current clinical trials are limited and don't address optimal strategies for recurring disease.
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Background: Prognostic factors for initial response of advanced cutaneous squamous cell carcinoma to cemiplimab treatment are lacking. Il-6 has been found to affect immune cell populations which impact tumor development. The aim was to investigate the prognostic significance of IL-6 serum levels before and during treatment.

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Background: Ewing sarcoma (ES) represents the second most common malignant bone tumor in children and young adults. ES is not a frequent finding in sites different from the skeletal. Common sites of appearance of ES are lower extremities, the pelvis, paravertebral spaces and head and neck.

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  • Gastric cancer (GC) is a serious disease, and early-onset cases (occurring in young individuals) pose unique challenges, representing about 5% of all GC cases.
  • Most early-onset GC cases are sporadic, and their increasing prevalence has heightened awareness and research interest in the medical community.
  • This overview focuses on non-hereditary early-onset GC, highlighting the need for personalized treatment approaches and exploring future directions in this area.
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Background: Thymic epithelial tumors (TETs) are frequently accompanied by Good Syndrome (GS), a rare immunodeficiency, characterized by hypogammaglobulinemia and peripheral B cell lymphopenia. TETs can be also associated to other immunological disorders, both immunodeficiency and autoimmunity.

Methods: In this study, we enrolled TET patients with GS to address differences between patients with or without associated autoimmune diseases (AD).

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Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland.

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Prostate cancer (PCa) treatment involves multiple strategies depending on the disease's stage. Androgen deprivation therapy (ADT) remains the gold standard for advanced and metastatic stages. Sleep quality has been suggested as being additionally influenced also by local radiotherapy, prostatectomy and androgen-receptor (AR)-targeted agents.

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  • This review evaluates the feasibility and side effects of high-dose chemotherapy (HDCT) versus standard dose chemotherapy (SDCT) for patients with mediastinal germ cell tumors (MGCTs), identifying factors that influence treatment choices.
  • MGCTs are rare and typically have a poor prognosis; HDCT has been explored since the 1970s as a potential alternative to SDCT for treating advanced germ cell tumor patients, but results on effectiveness and tolerability vary.
  • The review concludes that while HDCT is not yet a standard first-line treatment for advanced MGCTs, it may be a viable option for relapsed cases following careful patient assessment.
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Thymic epithelial tumors are rare tumors usually presenting as a mass located in the anterior mediastinum and/or with symptoms deriving from associated paraneoplastic syndromes. Unresectable platinum-refractory tumors are often treated with alternative regimens, including chemotherapeutic agents as well as chemo-free regimens. The most popular unconventional therapy is represented by the somatostatin analog octreotide, which can be used alone or with prednisone.

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Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM.

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  • Langerhans cell histiocytosis (LCH) is a rare disease with unpredictable symptoms and limited treatment options until recent advancements.
  • The use of targeted therapies, particularly imatinib—a tyrosine kinase inhibitor—has shown promise, especially in a case with brain involvement.
  • A study evaluating both PDGFRβ expression and the clinical effects of imatinib on LCH patients found significant PDGFRβ expression in some cases and long-lasting disease control in the treated patients.
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  • Cutaneous melanoma is a serious and often deadly disease that still presents challenges even with advancements in treatment, warranting the need for new therapeutic strategies.
  • Recent research highlights the role of epigenetics—specifically DNA methylation and chromatin changes—in melanoma development, progression, and resistance to current drugs like immune checkpoint and MAPK inhibitors.
  • The review provides an overview of current knowledge on epigenetics in melanoma and emphasizes potential new targets for developing epigenetic therapies, potentially in combination with existing treatments for advanced melanoma patients.
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