Complete regression of a previously untreated melanoma brain metastasis with ipilimumab.

Anecdotal cases of partial or complete responses have been reported after ipilimumab therapy for stage IV melanoma with brain metastasis treated earlier by surgery or radiosurgery. We report the first case of ipilimumab monotherapy resulting in durable complete remission of untreated, progressive brain metastases in a patient with stage IV melanoma. This case and earlier reports provide support for the further evaluation of ipilimumab in melanoma patients with brain metastasis.

Highly sensitive multivariable assay detection of melanocytic differentiation antigens and angiogenesis biomarkers in sentinel lymph nodes with melanoma micrometastases.

Objectives: To evaluate the prognostic value of melanocytic differentiation antigens and angiogenesis biomarkers in sentinel lymph nodes (SLNs) with melanoma micrometastases.

Design: Prognostic study of an inception cohort.

Setting: Academic research.

Kaposi's sarcoma in HIV-negative men having sex with men.

Background: Four epidemiologic forms of Kaposi's sarcoma have been described, all of which are associated with the human herpesvirus-8. In western countries, human herpesvirus-8 is more prevalent in homosexual men than in the general population, and anecdotal cases of Kaposi's sarcoma in HIV-negative homosexual men have been reported.

Patients And Methods: We included HIV-negative homosexual and bisexual male patients with histologically proven Kaposi's sarcoma in a retrospective study.

Chemoimmunotherapy of tumors: cyclophosphamide synergizes with exosome based vaccines.

Dendritic cell-derived exosomes (DEX) are nanomeric vesicles harboring MHC/peptide complexes capable of promoting primary T cell responses and tumor rejection in the presence of adjuvants. In this study, we show that, in the absence of adjuvants, DEX mediate potent Ag-dependent antitumor effects against preestablished tumors in mice pretreated with immunopotentiating dosing of cyclophosphamide. Cyclophosphamide could 1) abolish the suppressive function of CD4+CD25+Foxp3+ regulatory T cells, 2) markedly enhance the magnitude of secondary but not primary CTL responses induced by DEX vaccines, 3) synergize with DEX in therapy but not prophylaxis tumor models.

IL-2 production by dendritic cells is not critical for the activation of cognate and innate effectors in draining lymph nodes.

Dendritic cells (DC) are unique antigen-presenting cells capable of triggering NK cell effector functions and priming naive T cells in vivo. Microbial stimulation induces early IL-2 production by mouse DC. Previous reports demonstrated that IL-2 is enriched at the site of DC/T cell interaction and promotes allogeneic T cell proliferation.

The potential of exosomes in immunotherapy of cancer.

Dendritic-cell-derived exosomes (DEX) secreted after dendritic cell loading with tumor peptides were found to mediate tumor rejection in mice. This observation prompted us to demonstrate that MHC class I/peptide complexes harbored onto exosomal membranes were capable of priming cytotoxic T cells and to mediate rejection of tumors expressing the relevant antigens. Moreover, DEX also promote NK cell activation in immunocompetent mice and NK cell-dependent antitumor effects.

Exosomes as potent cell-free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection.

Ideal vaccines should be stable, safe, molecularly defined, and out-of-shelf reagents efficient at triggering effector and memory Ag-specific T cell-based immune responses. Dendritic cell-derived exosomes could be considered as novel peptide-based vaccines because exosomes harbor a discrete set of proteins, bear functional MHC class I and II molecules that can be loaded with synthetic peptides of choice, and are stable reagents that were safely used in pioneering phase I studies. However, we showed in part I that exosomes are efficient to promote primary MHC class I-restricted effector CD8(+) T cell responses only when transferred onto mature DC in vivo.

Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells.

Current immunization protocols in cancer patients involve CTL-defined tumor peptides. Mature dendritic cells (DC) are the most potent APCs for the priming of naive CD8(+) T cells, eventually leading to tumor eradication. Because DC can secrete MHC class I-bearing exosomes, we addressed whether exosomes pulsed with synthetic peptides could subserve the DC function consisting in MHC class I-restricted, peptide-specific CTL priming in vitro and in vivo.

Exosome-based immunotherapy.

Exosomes are small membrane vesicles originating from late endosomes and secreted by hematopoietic and epithelial cells in culture. Exosome proteic and lipid composition is unique and might shed some light into exosome biogenesis and function. Exosomes secreted from professional antigen-presenting cells (i.

[Exosomes and anti-tumour immunotherapy].

Exosomes are 60 to 90 nm membrane vesicles originating from late endosomes and secreted from most hematopoietic and epithelial cells in vitro. B cell derived-exosome antigenicity was first reported in 1996 in MHC class II restricted CD4+ T lymphocytes. In 1998, we reported that dendritic cell derived-exosomes are immunogenic in mice leading to tumor rejection.

Regression of CD8+ pseudolymphoma after HIV antiviral triple therapy.

To our knowledge, we report the first case of improvement of HIV-associated cutaneous CD8(+) pseudolymphoma with highly active antiretroviral therapy. This favors the hypothesis of a reactive cutaneous infiltration by HIV-specific cytotoxic T cells in this disease.

From the antigen-presenting cell to the antigen-presenting vesicle: the exosomes.

Exosomes are membrane vesicles of 30 to 100 nm in diameter, of endocytic origin, and are produced and secreted in vitro by living cells of diverse origin. In vivo and in vitro experiments suggest, from their particular proteomic composition, that exosomes are involved in the transfer of tumor antigens to antigen presenting cells, and in the stimulation of a specific immune response. In this review, we provide a molecular characterization of exosomes.

Malignant effusions and immunogenic tumour-derived exosomes.

Background: Exosomes derived from tumours are small vesicles released in vitro by tumour cell lines in culture supernatants. To assess the role of these exosomes in vivo, we examined malignant effusions for their presence. We also investigated whether these exosomes could induce production of tumour-specific T cells when pulsed with dendritic cells.

Report of a case of Schnitzler's syndrome treated successfully with interferon alpha 2b.

Schnitzler's syndrome (SS) is characterized by the association of generalized chronic urticaria, osteocondensation and monoclonal IgM gammopathy. Nonsteroidal anti-inflammatory drugs and systemic steroids are the most promising treatments. In our patient, they were ineffective.