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Melanoma: HELP
Articles by Caroline Aspord
Based on 10 articles published since 2008
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Between 2008 and 2019, C. Aspord wrote the following 10 articles about Melanoma.
 
+ Citations + Abstracts
1 Article The avidity of tumor-specific T cells amplified by a plasmacytoid dendritic cell-based assay can predict the clinical evolution of melanoma patients. 2018

Charles, Julie / Chaperot, Laurence / Revol, Bruno / Baudin, Marine / Mouret, Stephane / Hamon, Agnes / Leccia, Marie-Therese / Plumas, Joel / Aspord, Caroline. ·University Grenoble Alpes, Grenoble, France. · Immunobiology& Immunotherapy of Chronic Diseases, U1209, INSERM, La Tronche, France. · Dermatology, Pôle Pluridisciplinaire de Médecine, CHU Grenoble Alpes, Grenoble, France. · R&D Laboratory, Etablissement Français du Sang Rhone-Alpes, La Tronche, France. · Pharmacovigilance Department, CHU Grenoble Alpes, Grenoble, France. · Laboratoire Jean Kuntzmann, Universite Grenoble Alpes, Grenoble, France. ·Pigment Cell Melanoma Res · Pubmed #28741900.

ABSTRACT: The advent of immune checkpoint blockers and targeted therapies has changed the outcome of melanoma. However, many patients experience relapses, emphasizing the need for predictive and prognostic biomarkers. We developed a strategy based on plasmacytoid dendritic cells (pDCs) loaded with melanoma tumor antigens that allows eliciting highly efficient antitumor T-cell responses. We used it to investigate antitumor T-cell functionality in peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from melanoma patients. The pDCs elicited tumor-specific T cells in different proportions and displaying diverse functional features, dependent upon the stage of the disease, but independent of the histological parameters at diagnosis. Strikingly, the avidity of the MelA-specific T cells triggered by the pDCs was found to predict patient relapse time and overall survival. Our findings highlighted unexplored aspects of antitumor T-cell responsiveness in melanoma, and revealed for the first time the structural avidity of tumor-specific T cells as a crucial feature for predicting clinical evolution.

2 Article Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model. 2017

Karageorgis, Anastassia / Claron, Michaël / Jugé, Romain / Aspord, Caroline / Thoreau, Fabien / Leloup, Claire / Kucharczak, Jérôme / Plumas, Joël / Henry, Maxime / Hurbin, Amandine / Verdié, Pascal / Martinez, Jean / Subra, Gilles / Dumy, Pascal / Boturyn, Didier / Aouacheria, Abdel / Coll, Jean-Luc. ·INSERM U1209, Institut Albert Bonniot, 38706 La Tronche, France; Université Grenoble Alpes, 38000 Grenoble, France. · Université Grenoble Alpes, 38000 Grenoble, France; CNRS UMR 5250, ICMG FR2607, 38000 Grenoble, France. · Molecular Biology of the Cell Laboratory (LBMC), Ecole Normale Supérieure de Lyon, UMR 5239 CNRS - UCBL - ENS Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France. · Université Grenoble Alpes, 38000 Grenoble, France; EMR EFS-UGA-INSERM U1209- CNRS, Immunobiology and Immunotherapy of Chronic Diseases, 38706 La Tronche, France; EFS Rhone-Alpes, R&D Laboratory, 38701 La Tronche, France. · INSERM U1209, Institut Albert Bonniot, 38706 La Tronche, France; Université Grenoble Alpes, 38000 Grenoble, France; CNRS UMR 5250, ICMG FR2607, 38000 Grenoble, France. · CNRS UMR 5247, Institut des Biomolécules Max Mousseron IBMM, 34095 Montpellier, France. · CNRS UMR 5250, ICMG FR2607, 38000 Grenoble, France; CNRS UMR 5247, Institut des Biomolécules Max Mousseron IBMM, 34095 Montpellier, France. · Molecular Biology of the Cell Laboratory (LBMC), Ecole Normale Supérieure de Lyon, UMR 5239 CNRS - UCBL - ENS Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France; Institut des Sciences de l'Evolution de Montpellier (ISEM), UMR 5554, Université de Montpellier, CNRS, IRD, EPHE, Place Eugène Bataillon, 34095 Montpellier, France. Electronic address: jean-luc.coll@univ-grenoble-alpes.fr. · INSERM U1209, Institut Albert Bonniot, 38706 La Tronche, France; Université Grenoble Alpes, 38000 Grenoble, France. Electronic address: abdel.aouacheria@umontpellier.fr. ·Mol Ther · Pubmed #28153100.

ABSTRACT: Melanoma is a highly metastatic and deadly form of cancer. Invasive melanoma cells overexpress integrin α

3 Article Melanoma dormancy in a mouse model is linked to GILZ/FOXO3A-dependent quiescence of disseminated stem-like cells. 2016

Touil, Yasmine / Segard, Pascaline / Ostyn, Pauline / Begard, Severine / Aspord, Caroline / El Machhour, Raja / Masselot, Bernadette / Vandomme, Jerome / Flamenco, Pilar / Idziorek, Thierry / Figeac, Martin / Formstecher, Pierre / Quesnel, Bruno / Polakowska, Renata. ·Inserm UMR-S1172 Centre de Recherche Jean Pierre Aubert (JPArc), Institut pour la Recherche sur le Cancer de Lille (IRCL), 1 Place de Verdun, 59045 Lille, France. · Faculté de Médecine, Université de Lille, 59000 Lille, France. · SIRIC ONCOLille, Lille, France. · Institut A. Bonniot, Ontogenèse et Oncogenèse Moléculaires, UMR EFS-UJF-INSERM 823, Immunobiology and Immunotherapy of Cancers, Grenoble, France. · Faculté de Chirurgie Dentaire, Université de Lille, 59000 Lille, France. · Plateforme de Génomique Fonctionnelle, IRCL, 59045 Lille, France. · Cancéropôle Nord-Ouest, 6 rue du Professeur Laguesse, 59045 Lille, France. · Service des Maladies du Sang, CHRU de Lille, 59037 Lille, France. ·Sci Rep · Pubmed #27465291.

ABSTRACT: Metastatic cancer relapses following the reactivation of dormant, disseminated tumour cells; however, the cells and factors involved in this reactivation are just beginning to be identified. Using an immunotherapy-based syngeneic model of melanoma dormancy and GFP-labelled dormant cell-derived cell lines, we determined that vaccination against melanoma prevented tumour growth but did not prevent tumour cell dissemination or eliminate all tumour cells. The persistent disseminated melanoma tumour cells were quiescent and asymptomatic for one year. The quiescence/activation of these cells in vitro and the dormancy of melanoma in vivo appeared to be regulated by glucocorticoid-induced leucine zipper (GILZ)-mediated immunosuppression. GILZ expression was low in dormant cell-derived cultures, and re-expression of GILZ inactivated FOXO3A and its downstream target, p21CIP1. The ability of dormancy-competent cells to re-enter the cell cycle increased after a second round of cellular dormancy in vivo in association with shortened tumour dormancy period and faster and more aggressive melanoma relapse. Our data indicate that future cancer treatments should be adjusted according to the stage of disease progression.

4 Article pDCs efficiently process synthetic long peptides to induce functional virus- and tumour-specific T-cell responses. 2014

Aspord, Caroline / Leloup, Claire / Reche, Sabine / Plumas, Joel. ·R&D Laboratory, Etablissement Français du Sang Rhone-Alpes, Grenoble, France; Immunobiology & Immunotherapy of Cancers, University Joseph Fourier, Grenoble, France. ·Eur J Immunol · Pubmed #25043392.

ABSTRACT: Robust cell-mediated immunity is required for immune control of tumours and protection from viral infections, with both CD4(+) and CD8(+) T cells playing a pivotal role. Synthetic long peptides (SLPs) represent an attractive way to induce such combined responses, as they contain both class I and class II epitopes. The ability of plasmacytoid dendritic cells (pDCs) to cross-present SLPs has not yet been investigated; yet, pDCs play a critical role in shaping immune responses and have emerged as novel vectors for immunotherapy. Using overlapping 15-mer peptide pools covering the entire sequence of CMVpp65 and MelA, representing a viral disease (cytomegalovirus, CMV) and a tumour (melanoma), respectively, we showed that human pDCs can effectively process SLPs. Our results demonstrated that pDCs potently cross-present virus- and tumour-derived SLPs and cross-prime broad-ranging, effective and long-lived CD4(+) and CD8(+) T-cell responses, triggering more efficient immune responses than short peptide loaded pDCs. This ability required intracellular processing by the proteasome and was enhanced by co-exposure to TLR7/9-L. Combining SLPs with pDCs represents a powerful immunotherapeutic strategy to elicit potent immune responses, which are required for clinical success in cancers and viral infections.

5 Article Imiquimod inhibits melanoma development by promoting pDC cytotoxic functions and impeding tumor vascularization. 2014

Aspord, Caroline / Tramcourt, Laetitia / Leloup, Claire / Molens, Jean-Paul / Leccia, Marie-Therese / Charles, Julie / Plumas, Joel. ·R&D Laboratory, Etablissement Français du Sang Rhône-Alpes, La Tronche, France; University Joseph Fourier, Grenoble, France; Immunobiology & Immunotherapy of Cancers, U823, INSERM, La Tronche, France. Electronic address: carolineaspord@yahoo.com. · R&D Laboratory, Etablissement Français du Sang Rhône-Alpes, La Tronche, France; University Joseph Fourier, Grenoble, France; Immunobiology & Immunotherapy of Cancers, U823, INSERM, La Tronche, France. · University Joseph Fourier, Grenoble, France; Immunobiology & Immunotherapy of Cancers, U823, INSERM, La Tronche, France; Department of Dermatology, Grenoble University Hospital, Grenoble, France. ·J Invest Dermatol · Pubmed #24751730.

ABSTRACT: Imiquimod (IMQ) is a synthetic Toll-like receptor (TLR7/8) ligand that can trigger antiviral and antitumor activities. Despite evidence of potent therapeutic effects, the clinical use of IMQ in melanoma is impeded by incomplete understanding of its mechanisms of action. Mice and humans differ in many aspects of immunity, including TLR7 expression patterns, thus impeding the use of mouse models in translating discoveries into clinical applications. In this article, we investigated the mechanisms behind IMQ effects in vivo in a human context of melanoma and immunity using an innovative melanoma-bearing humanized mouse model. In this model, IMQ strongly inhibited melanoma tumor development through prompt mobilization of plasmacytoid dendritic cells and by triggering their cytotoxic functions, and through upregulation of expression of type 1 IFN response genes. IMQ also drastically impeded tumor vascularization by inducing the downregulation of angiogenic factors vascular endothelial growth factor, angiogenin, IL-8, and fibroblast growth factor. Our results revealed the short- and long-term multifactorial effects of IMQ converging toward inhibition of melanoma development. By providing a better understanding of the mechanisms of action of IMQ in melanoma, our study opens the way for its further clinical use in the treatment of metastatic melanoma.

6 Article Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL. 2013

Aspord, Caroline / Leccia, Marie-Therese / Charles, Julie / Plumas, Joel. ·Authors' Affiliations: Department of Dermatology, Grenoble University Hospital, Grenoble, France. ·Cancer Immunol Res · Pubmed #24778133.

ABSTRACT: Even though melanoma is considered to be one of the most immunogenic solid tumors, handling its development remains a challenge. The basis for such escape from antitumor immune control has not yet been documented. Plasmacytoid dendritic cells (pDC) are emerging as crucial but still enigmatic cells in cancer. In melanoma, the function of tumor-infiltrating pDCs remains poorly explored. We investigated the pathophysiologic role of pDCs in melanoma, both ex vivo from a large cohort of melanoma patients and in vivo in melanoma-bearing humanized mice. pDCs were found in high proportions in cutaneous melanoma and tumor-draining lymph nodes, yet associated with poor clinical outcome. We showed that pDCs migrating to the tumor microenvironment displayed particular features, subsequently promoting proinflammatory Th2 and regulatory immune profiles through OX40L and ICOSL expression. Elevated frequencies of interleukin (IL)-5-, IL-13- and IL-10-producing T cells in patients with melanoma correlated with high proportions of OX40L- and ICOSL-expressing pDCs. Strikingly TARC/CCL17, MDC/CCL22, and MMP-2 found in the melanoma microenvironment were associated with pDC accumulation, OX40L and ICOSL modulation, and/or early relapse. Thus, melanoma actively exploits pDC plasticity to promote its progression. By identifying novel insights into the mechanism of hijacking of immunity by melanoma, our study exposes potential for new therapeutic opportunities.

7 Article HLA-A(*)0201(+) plasmacytoid dendritic cells provide a cell-based immunotherapy for melanoma patients. 2012

Aspord, Caroline / Leccia, Marie-Therese / Salameire, Dimitri / Laurin, David / Chaperot, Laurence / Charles, Julie / Plumas, Joel. ·Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France. Electronic address: carolineaspord@yahoo.com. · University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; Department of Dermatology, Michallon Hospital, Pôle Pluridisciplinaire de Médecine, Grenoble, France. · University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; Anatomo-cytopathology, Michallon Hospital, Grenoble, France. · Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France. · Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; University College London, Cancer Institute, London, UK. ·J Invest Dermatol · Pubmed #22696054.

ABSTRACT: Several sources of evidence suggest that tumor-specific T cells have the potential to control melanoma tumors. Current active and adoptive therapeutic approaches to elicit such T cells are either not sufficiently clinically efficient or require fastidious processes that impede their extensive clinical use. As plasmacytoid dendritic cells (pDCs) have a crucial role in triggering antitumor immunity especially in melanoma, we explored their potential as a cell-based approach for melanoma immunotherapy. An irradiated human HLA-A(*)0201(+) pDC line loaded with peptides derived from the major melanoma tumor antigens, MelA/MART-1, gp100/pmel17, tyrosinase, and MAGE-A3, was used to trigger functional multi-specific T cells ex vivo from peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from stage I-IV HLA-A(*)0201(+) melanoma patients. pDCs loaded with melanoma-derived peptides promptly induced high levels of melanoma tumor-specific T cells from both sources. pDC-primed central/effector memory antitumor T cells were highly functional as indicated by the specific IFNγ secretion and membrane CD107 expression upon stimulation. Cells also exhibited strong cytotoxicity toward semi-allogeneic melanoma cells and patient-derived tumor cells. The simple design and potent efficacy of this promising approach provides a preclinical basis for the development of a pDC-based vaccine and an alternative means to produce tumor-specific T cells for adoptive cellular immunotherapy in melanoma patients.

8 Article [GENiusVac, a novel antitumor vaccine strategy based on allogeneic plasmacytoid dendritic cells]. 2011

Aspord, C / Charles, J / Leccia, M-T / Laurin, D / Richard, M-J / Chaperot, L / Plumas, J. ·Inserm U823, Établissement français du sang (EFS) Rhone-Alpes, R&D Laboratory, 38701 La Tronche, France. carolineaspord@yahoo.com ·Rev Med Interne · Pubmed #21429635.

ABSTRACT: The development of effective vaccines against cancer and viruses still remains a challenge. Many immunotherapeutic strategies have been developed but without sufficient therapeutic success. Plasmacytoid dendritic cells (pDC) play a crucial role in antitumor and antiviral responses. Despite their outstanding functional properties, their therapeutic potential has not yet been worked out. We propose a new immunotherapeutic strategy based on a pDC cell line irradiated and pulsed with tumor or viral antigens. GENiusVac allows the induction of multispecific and highly functional cytotoxic cell responses directed against viral or tumor targets. We demonstrated the potential of this strategy in vitro, its therapeutic efficacy in vivo in a humanized mouse model, and its clinical relevance ex vivo from melanoma patients' cells. GENiusVac highlights pDCs as potent vector of immunotherapy and provide a way to exploit them in cell therapy to fight cancer or chronic viral infections.

9 Article A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells. 2010

Aspord, Caroline / Charles, Julie / Leccia, Marie-Therese / Laurin, David / Richard, Marie-Jeanne / Chaperot, Laurence / Plumas, Joel. ·Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France. carolineaspord@yahoo.com ·PLoS One · Pubmed #20454561.

ABSTRACT: BACKGROUND: The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs) in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy. METHODS AND FINDINGS: Stimulation of PBMC from HLA-A*0201(+) donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer(+) CD8 T cells). The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment. CONCLUSIONS: These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.

10 Article Characterization of circulating dendritic cells in melanoma: role of CCR6 in plasmacytoid dendritic cell recruitment to the tumor. 2010

Charles, Julie / Di Domizio, Jérémy / Salameire, Dimitri / Bendriss-Vermare, Nathalie / Aspord, Caroline / Muhammad, Ramzan / Lefebvre, Christine / Plumas, Joël / Leccia, Marie-Thérèse / Chaperot, Laurence. ·INSERM U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des Cancers, Université Joseph Fourier, R&D Laboratory, EFS Rhônes-Alpes, 29 Avenue Maquis du Gresivaudan, La Tronche, France. ·J Invest Dermatol · Pubmed #20220766.

ABSTRACT: Dendritic cells (DCs) are central cells in the development of antitumor immune responses, but the number and function of these cells can be altered in various cancers. Whether these cells are affected during the development of melanoma is not known. We investigated the presence, phenotype, and functionality of circulating myeloid DCs (MDCs) and plasmacytoid DCs (PDCs) in newly diagnosed melanoma patients, compared to controls. The frequencies of PDCs and MDCs were equivalent in melanoma patients as compared with normal subjects. Both circulating DC subsets were immature, but on ex vivo stimulation with R848 they efficiently upregulated their expression of costimulatory molecules. We found that circulating DCs from melanoma patients and controls displayed similar pattern of expression of the chemokine receptors CXCR3, CXCR4, CCR7, and CCR10. Strikingly, PDCs from melanoma patients expressed higher levels of CCR6 than control PDCs, and were able to migrate toward CCL20. Further data showed that CCR6-expressing PDCs were present in melanoma primary lesions, and that CCL20 was produced in melanoma tumors. These results suggest that PDCs and MDCs are functional in melanoma patients at the time of diagnosis, and that CCL20 may participate to their recruitment from the blood to the tumor.