Extracellular adenosine metabolism in immune cells in melanoma
Abstract Malignant melanoma is characterized by the development of chronic inflammation in the tumor microenvironment, which leads to a strong immunosuppression associated with a rapid tumor progression. Adenosine is considered as one of the main immunosuppressive factors in the tumor environment. It is produced via enzymatic hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 localized on cell surface. Using the ret transgenic mouse melanoma model that closely mimics human melanoma, we demonstrated an increased frequency of ectonucleotidase-positive myeloid-derived suppressor cells (MDSCs) in mela...
Source: Cancer Immunology, Immunotherapy - September 25, 2014 Category: Cancer & Oncology Source Type: research

Erratum to: Immunologic hierarchy, class II MHC promiscuity, and epitope spreading of a melanoma helper peptide vaccine
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 25, 2014 Category: Cancer & Oncology Source Type: research

Novel N-amidinopiperidine-based proteasome inhibitor preserves dendritic cell functionality and rescues their Th1-polarizing capacity in Ramos-conditioned tumor environment
Abstract The tumor microenvironment represents a burden that hampers the proper activation of immune cells, including the dendritic cells (DCs). It is, therefore, desired that the important characteristics of a given anticancer drug candidate be seen as consisting not solely of its antitumor properties, but that it also lacks potential side effects that could additionally constrain the development and function of immune cells associated with tumor immunity. We have previously identified compounds with a N-amidinopiperidine scaffold that selectively induce apoptosis in Burkitt’s lymphoma cells through pro...
Source: Cancer Immunology, Immunotherapy - September 25, 2014 Category: Cancer & Oncology Source Type: research

Erratum to: Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 25, 2014 Category: Cancer & Oncology Source Type: research

CTLA4 blockade in mesothelioma: finally a competing strategy over cytotoxic/target therapy?
Abstract No second-line treatment significantly prolongs the survival of malignant mesothelioma patients who have a high unmet medical need. Here, we comment on the therapeutic potential of cytotoxic T-lymphocyte-associated protein (CTLA)4-blockade by the anti-CTLA4 monoclonal antibody (mAb) tremelimumab of refractory malignant mesothelioma patients. We also focus on the critical role of an accurate tumor assessment in the course of treatment with immunomodulating mAb. Finally, treatment with potentially effective, second-generation checkpoint(s) inhibiting mAb, as well future combination strategies in this de...
Source: Cancer Immunology, Immunotherapy - September 19, 2014 Category: Cancer & Oncology Source Type: research

Successful treatment with Ipilimumab and Interleukin-2 in two patients with metastatic melanoma and systemic autoimmune disease
Abstract Two patients were treated with immunotherapy for metastatic malignant melanoma (MM) despite suffering from systemic autoimmune disease, i.e., ulcerative colitis (UC) and Behcets disease (BD), respectively. Both patients benefitted from the treatment. The patient with UC achieved partial remission of all measurable parameters after treatment with Ipilimumab, while the patient with BD achieved a complete remission of MM after treatment with Interleukin-2 (IL-2) and Interferon-α (IFN-α). Moreover, no aggravation of symptoms related to the autoimmune diseases was seen during treatment, in cont...
Source: Cancer Immunology, Immunotherapy - September 17, 2014 Category: Cancer & Oncology Source Type: research

Sequential immune monitoring in patients with melanoma and renal cell carcinoma treated with high-dose interleukin-2: immune patterns and correlation with outcome
Abstract Interleukin-2 (IL-2) therapy leads to clinically relevant responses in 10–16 % of patients with metastatic melanoma (MMEL) or 10–30 % of patients with metastatic renal cell carcinoma (MRCC). To date, no biomarkers have been validated to identify patients who are likely to respond. We hypothesized that changes in T cell subset distribution in patients undergoing IL-2 therapy may correlate with treatment outcomes. Immune profiles of 64 patients (27-MMEL, 37-MRCC) were evaluated using flow cytometry at baseline, during (≥three doses) and at the end of treatment cycle (30 ±...
Source: Cancer Immunology, Immunotherapy - September 10, 2014 Category: Cancer & Oncology Source Type: research

Identification and characterization of a cytotoxic T-lymphocyte agonist epitope of brachyury, a transcription factor involved in epithelial to mesenchymal transition and metastasis
Abstract The transcription factor brachyury is a major driver of epithelial to mesenchymal transition in human carcinoma cells. It is overexpressed in several human tumor types versus normal adult tissues, except for testes and thyroid. Overexpression is associated with drug resistance and poor prognosis. Previous studies identified a brachyury HLA-A2 cytotoxic T-lymphocyte epitope. The studies reported here describe an enhancer epitope of brachyury. Compared to the native epitope, the agonist epitope: (a) has enhanced binding to MHC class I, (b) increased the IFN-γ production from brachyury-specific T cells...
Source: Cancer Immunology, Immunotherapy - September 4, 2014 Category: Cancer & Oncology Source Type: research

Interactions between neutrophils and non-small cell lung cancer cells: enhancement of tumor proliferation and inflammatory mediator synthesis
In this study, we characterized the effect of isolated human neutrophils on proliferation of the non-small cell lung cancer (NSCLC) cell line A549 and analyzed the impact of A549–neutrophil interactions on inflammatory mediator generation in naive and lipopolysaccharide (LPS)-exposed cell cultures. Co-incubation of A549 cells with neutrophils induced proliferation of resting and LPS-exposed A549 cells in a dose-dependent manner. In transwell-experiments, this effect was demonstrated to depend on direct cell-to-cell contact. This pro-proliferative effect of neutrophils on A549 cells could be attenuated by inhibition o...
Source: Cancer Immunology, Immunotherapy - September 4, 2014 Category: Cancer & Oncology Source Type: research

High placenta-specific 1/low prostate-specific antigen expression pattern in high-grade prostate adenocarcinoma
Conclusion Our findings on differential expression of PLAC1 in PCa plus its positive association with Gleason score and negative correlation with PSA expression highlight the potential usefulness of PLAC1 for targeted PC therapy especially for patients with advanced disease. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 4, 2014 Category: Cancer & Oncology Source Type: research