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The immune cell landscape of metastatic uveal melanoma correlates with overall survival.
Tosi, Anna; Cappellesso, Rocco; Dei Tos, Angelo Paolo; Rossi, Valentina; Aliberti, Camillo; Pigozzo, Jacopo; Fabozzi, Alessio; Sbaraglia, Marta; Blandamura, Stella; Del Bianco, Paola; Chiarion-Sileni, Vanna; Rosato, Antonio.
Afiliação
  • Tosi A; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
  • Cappellesso R; Pathological Anatomy Unit, Padova University Hospital, Padova, Italy.
  • Dei Tos AP; Pathological Anatomy Unit, Padova University Hospital, Padova, Italy.
  • Rossi V; Department of Medicine (DIMED), Surgical Pathology Unit, University of Padova, Padova, Italy.
  • Aliberti C; Immunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128, Padova, Italy.
  • Pigozzo J; Departement of Diagnostic & Interventive Radiology-Pederzoli Hospital, Peschiera, VR, Italy.
  • Fabozzi A; Melanoma Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
  • Sbaraglia M; Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
  • Blandamura S; Pathological Anatomy Unit, Padova University Hospital, Padova, Italy.
  • Del Bianco P; Department of Medicine (DIMED), Surgical Pathology Unit, University of Padova, Padova, Italy.
  • Chiarion-Sileni V; Clinical Research Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
  • Rosato A; Melanoma Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
J Exp Clin Cancer Res ; 40(1): 154, 2021 May 04.
Article em En | MEDLINE | ID: mdl-33947438
BACKGROUND: Uveal melanoma (UM) represents the most common primary intra-ocular malignancy in adults. Up to 50% of the patients develop distant metastases within 10 years from diagnosis, with the liver as the most common site. Upon metastatization, life expectancy strongly reduces and immune checkpoint inhibitors that prove effective in cutaneous melanoma do not modify clinical outcome. To date, few studies have focused on deciphering the immunomodulatory features of metastatic UM microenvironment, and there are no prognostic models for clinical use. This highlights the urgent need to understand the delicate interplay between tumor and immune cells acting at the site of metastasis. METHODS: We collected a patient cohort comprising 21 metastatic UM patients. Hepatic and extra-hepatic UM metastasis samples were studied by multiplex immunofluorescence to assess the tumor immune cell composition. Quantitative analyses were performed to correlate immune cell densities with treatment response, metastasis site and patient survival. RESULTS: Compared to patients with progressive disease, those with controlled disease had a higher intra-tumoral/peritumoral ratio of CD8 + Granzyme B+ cells, higher density of intra-tumoral CD8+ cytotoxic T lymphocytes (CTL) and an increased percentage of UM cells in close proximity to T lymphocytes, reflecting a role of tumor-killing T cells in the disease. In liver metastases (LM), the intra-tumoral densities of CD163+ tumor-associated macrophages (TAM) and of total CD8+ T cells were higher than in extra-hepatic UM metastases, but the percentage of Granzyme B+ CTL was lower. Moreover, LM displayed more UM cells adjacent to both CTL and TAM, and also more T cells in proximity to TAM, all signs of an impaired immune response. The percentage of activated CTL within the tumor represented a prognostic indicator, as patients with a higher intra-tumoral percentage of CD8 + Granzyme B+ cells had the better outcome. A temptative Immunoscore was generated and proved capable to stratify patients with improved survival. Finally, CD4 + FoxP3+ T cells appeared a crucial population for response to immunotherapy. CONCLUSION: The results of this study underly the clinical relevance and functional importance of composition and localization of antitumor effector cells for the progression of UM metastasis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 6_ODS3_enfermedades_notrasmisibles Problema de saúde: 6_malignant_skin_melanoma Assunto principal: Neoplasias Uveais / Melanoma Tipo de estudo: Prognostic_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Exp Clin Cancer Res Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 6_ODS3_enfermedades_notrasmisibles Problema de saúde: 6_malignant_skin_melanoma Assunto principal: Neoplasias Uveais / Melanoma Tipo de estudo: Prognostic_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Exp Clin Cancer Res Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Itália
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