An actionable axis linking NFATc2 to EZH2 controls the EMT-like program of melanoma cells.

Discovery of new actionable targets and functional networks in melanoma is an urgent need as only a fraction of metastatic patients achieves durable clinical benefit by targeted therapy or immunotherapy approaches. Here we show that NFATc2 expression is associated with an EMT-like transcriptional program and with an invasive melanoma phenotype, as shown by analysis of melanoma cell lines at the mRNA and protein levels, interrogation of the TCGA melanoma dataset and characterization of melanoma lesions by immunohistochemistry. Gene silencing or pharmacological inhibition of NFATc2 downregulated EMT-related genes and AXL, and suppressed c-Myc, FOXM1, and EZH2.

Early Effector T Lymphocytes Coexpress Multiple Inhibitory Receptors in Primary Non-Small Cell Lung Cancer.

Clinical efficacy of PD-1/PD-L1 targeting relies upon the reactivation of tumor-specific but functionally impaired PD-1 T cells present before therapy. Thus, analyzing early-stage primary tumors may reveal the presence of T cells that are not yet functionally impaired. In this study, we report that activated (HLA-DR) T cells with an effector memory (T) profile are enriched in such lesions.

Molecular subtyping of metastatic melanoma based on cell ganglioside metabolism profiles.

Background: In addition to alterations concerning the expression of oncogenes and onco-suppressors, melanoma is characterized by the presence of distinctive gangliosides (sialic acid carrying glycosphingolipids). Gangliosides strongly control cell surface dynamics and signaling; therefore, it could be assumed that these alterations are linked to modifications of cell behavior acquired by the tumor. On these bases, this work investigated the correlations between melanoma cell ganglioside metabolism profiles and the biological features of the tumor and the survival of patients.

NFATc2 is a potential therapeutic target in human melanoma.

The identification of intracellular signaling pathways that promote cell proliferation and resistance to cell death may lead to the development of improved treatment for advanced melanoma. Here we show that the calcineurin/nuclear factor of activated T cells c2 (NFATc2) pathway has an antiapoptotic role in melanoma cells. Expression of NFATc2 was constitutive in vitro and in vivo in human melanoma, and cyclosporin A (CsA) treatment of melanoma cells led to downmodulation of NFATc2.

Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunologic responses in indolent B-cell lymphoma patients with relapsed and measurable disease: a pilot study.

Eighteen relapsed patients with measurable indolent non-Hodgkin lymphoma (NHL) were vaccinated with dendritic cells (DCs) loaded with killed autologous tumor cells. Six patients had objective clinical responses including 3 continuous complete responses (CRs) and 3 partial responses (PRs), with a median follow up of 50.5 months.

Regulation of breast cancer response to chemotherapy by fibulin-1.

Doxorubicin treatment was found to augment the expression of the extracellular matrix (ECM) protein fibulin-1 in cultured human breast cancer cell lines and in MDA-MB-361 tumors grown in athymic mice. Doxorubicin was also found to augment tumor expression of the fibulin-1-binding proteins fibronectin and laminin-1. Growth of breast cancer cell lines on Matrigel, an ECM extract containing fibulin-1 and laminin-1, resulted in lower levels of doxorubicin-induced apoptosis as compared with controls.

Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with gammac cytokines.

The unfavorable clinical evolution in indolent non-Hodgkin lymphomas suggests defective control of neoplastic growth by the immune system. To address this issue, we evaluated phenotype, function, and maturation profile of CD4(+) and CD8(+) T cells from peripheral-blood, lymph nodes, or bone marrow of patients with B-cell non-Hodgkin lymphoma (NHL) at diagnosis. T cells from these patients frequently showed an activated but apoptosis-prone phenotype with low frequency of tumor-reactive T cells showing a TH2/Tc2 functional profile in the response to autologous tumor.

Boosting T cell-mediated immunity to tyrosinase by vaccinia virus-transduced, CD34(+)-derived dendritic cell vaccination: a phase I trial in metastatic melanoma.

Purpose: Six American Joint Committee on Cancer stage IV melanoma patients were enrolled into a Phase I study of vaccination with autologous CD34(+)-derived dendritic cells transduced with a modified vaccinia Ankara virus encoding human tyrosinase gene (MVA-hTyr).

Experimental Design: Patients received a first intravenous injection of 1 x 10(8) MVA-hTyr-transduced dendritic cells, followed by three s.c.

Immunological and pathobiological roles of fibulin-1 in breast cancer.

Fibulin-1 (Fbln-1) is an immunogenic breast cancer-related glycoprotein identified by serological analysis of cDNA expression library (SEREX) strategy. Here, we show that dendritic cells from two breast cancer patients elicited a CD4(+)-mediated T-cell response to Fbln-1 presentation. In both patients, an antibody response to Fbln-1 was also found.