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Melanoma: HELP
Articles by Laurence Chaperot
Based on 9 articles published since 2010
(Why 9 articles?)
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Between 2010 and 2020, L. Chaperot wrote the following 9 articles about Melanoma.
 
+ Citations + Abstracts
1 Review Plasma Circulating Tumor DNA Levels for the Monitoring of Melanoma Patients: Landscape of Available Technologies and Clinical Applications. 2017

Busser, Benoit / Lupo, Julien / Sancey, Lucie / Mouret, Stéphane / Faure, Patrice / Plumas, Joel / Chaperot, Laurence / Leccia, Marie Thérèse / Coll, Jean Luc / Hurbin, Amandine / Hainaut, Pierre / Charles, Julie. ·Biochemistry Pharmacology and Toxicology Department, Grenoble University Hospital, Grenoble, France. · Institute for Advanced Biosciences, UGA/INSERM U1209/CNRS UMR5309, Grenoble, France. · Virology Laboratory, Grenoble University Hospital, Grenoble, France. · Institut de Biologie Structurale, CEA-CNRS UMR 5075/UGA, Grenoble, France. · Dermatology Unit, Grenoble University Hospital, Grenoble, France. · UGA, Laboratory of Hypoxy Physiopathology Study, INSERM U1042, Grenoble, France. · EFS Rhone-Alpes-Auvergne, Grenoble, France. ·Biomed Res Int · Pubmed #28484715.

ABSTRACT: Melanoma is a cutaneous cancer with an increasing worldwide prevalence and high mortality due to unresectable or metastatic stages. Mutations in

2 Article An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial. 2020

Charles, Julie / Chaperot, Laurence / Hannani, Dalil / Bruder Costa, Juliana / Templier, Isabelle / Trabelsi, Sabiha / Gil, Hugo / Moisan, Anaick / Persoons, Virginie / Hegelhofer, Harald / Schir, Edith / Quesada, Jean-Louis / Mendoza, Christophe / Aspord, Caroline / Manches, Olivier / Coulie, Pierre G / Khammari, Amir / Dreno, Brigitte / Leccia, Marie-Thérèse / Plumas, Joel. ·Immunobiology and Immunotherapy of Chronic Diseases, Institute for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France. · Dermatology Department, Pôle Pluridisciplinaire de Médecine, CHU Grenoble Alpes, Grenoble, France. · R&D Laboratory, Etablissement Français du Sang Auvergne-Rhône-Alpes, Grenoble, France. · Immune checkpoint inhibitors, PDCline Pharma, Grenoble. · Pathology Department, Institut de Biologie et Pathologie, CHU Grenoble Alpes, Grenoble, France. · Cell Therapy and Engineering Unit, Etablissement Français du Sang Auvergne-Rhône-Alpes, Saint Ismier, France. · Délégation à la Recherche Clinique et à l'Innovation, CHU Grenoble Alpes, Grenoble, France. · Centre d'investigation Clinique, CHU Grenoble Alpes, Grenoble, France. · de Duve Institute, Université Catholique de Louvain, Brussels, Belgium. · Onco-dermatology Department, CHU Nantes, CIC 1413, CRCINA, Nantes University, Nantes, France. ·Oncoimmunology · Pubmed #32313721.

ABSTRACT: The efficacy of immune checkpoint inhibitors has been shown to depend on preexisting antitumor immunity; thus, their combination with cancer vaccines is an attractive therapeutic approach. Plasmacytoid dendritic cells (PDC) are strong inducers of antitumor responses and represent promising vaccine candidates. We developed a cancer vaccine approach based on an allogeneic PDC line that functioned as a very potent antigen-presenting cell in pre-clinical studies. In this phase Ib clinical trial, nine patients with metastatic stage IV melanoma received up to 60 million irradiated PDC line cells loaded with 4 melanoma antigens, injected subcutaneously at weekly intervals. The primary endpoints were safety and tolerability. The vaccine was well tolerated and no serious vaccine-induced side effects were recorded. Strikingly, there was no allogeneic response toward the vaccine, but a significant increase in the frequency of circulating anti-tumor specific T lymphocytes was observed in two patients, accompanied by a switch from a naïve to memory phenotype, thus demonstrating priming of antigen-specific T-cells. Signs of clinical activity were observed, including four stable diseases according to IrRC and vitiligoïd lesions. Four patients were still alive at week 48. We also demonstrate the in vitro enhancement of specific T cell expansion induced by the synergistic combination of peptide-loaded PDC line with anti-PD-1, as compared to peptide-loaded PDC line alone. Taken together, these clinical observations demonstrate the ability of the PDC line based-vaccine to prime and expand antitumor CD8+ responses in cancer patients. Further trials should test the combination of this vaccine with immune checkpoint inhibitors.

3 Article T-cell receptor diversity as a prognostic biomarker in melanoma patients. 2020

Charles, Julie / Mouret, Stephane / Challende, Isabelle / Leccia, Marie-Therese / De Fraipont, Florence / Perez, Solene / Plantier, Nadia / Plumas, Joel / Manuel, Manuarii / Chaperot, Laurence / Aspord, Caroline. ·Immunobiology and Immunotherapy of Chronic Diseases, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Université Grenoble Alpes, Grenoble, France. · Dermatology Clinic, Grenoble University Hospital, Grenoble, France. · Department of Biochemistry of Cancers and Biotherapies, Grenoble University Hospital, Grenoble, France. · ImmunID, Grenoble, France. · R&D-Laboratory, Etablissement Français du Sang Auvergne Rhone-Alpes, Grenoble, France. ·Pigment Cell Melanoma Res · Pubmed #31971658.

ABSTRACT: There is increasing evidence that T-cell receptor (TCR) repertoire diversity can be a predictive biomarker of immune responses in cancer patients. However, the characteristics of the T-cell repertoire together with its prognostic significance in melanoma patients and impact on disease progression remain unknown. We investigated the combinatorial TCR repertoire diversity by semi-quantitative multi-N-plex PCR in peripheral blood samples from 44 melanoma patients together with seven matched metastatic lymph nodes and explored its potential predictive value on clinical prognosis. The diversity was quantified by calculating both richness (number of different specificities) and evenness (relative abundance of the different specificities). Our results revealed that a higher TCR repertoire diversity in blood of patients was associated with a longer PFS, while divpenia (low repertoire diversity) was linked with poor prognosis. The diversity was significantly higher in patients undergoing late relapse and long survival compared to patients who progressed rapidly. Interestingly, the TCR repertoire diversity in tumor may have a potential prognostic value. Thus, our study highlights that the TCR repertoire diversity is a prognostic indicator of clinical outcome in patients with melanoma.

4 Article The features of circulating and tumor-infiltrating γδ T cells in melanoma patients display critical perturbations with prognostic impact on clinical outcome. 2019

Girard, Pauline / Charles, Julie / Cluzel, Camille / Degeorges, Emmanuelle / Manches, Olivier / Plumas, Joel / De Fraipont, Florence / Leccia, Marie-Therese / Mouret, Stephane / Chaperot, Laurence / Aspord, Caroline. ·Etablissement Français du Sang Auvergne Rhone-Alpes, R&D-Laboratory, Grenoble, France. · University Grenoble Alpes, EMR EFS-UGA-INSERM U1209- CNRS, Immunobiology & Immunotherapy of Chronic Diseases, Grenoble, France. · Dermatology clinic, Grenoble University Hospital, Grenoble, France. · pDCline Pharma, Grenoble, France. · Department of Biochemistry of Cancers and Biotherapies, Grenoble University Hospital, Grenoble, France. ·Oncoimmunology · Pubmed #31413911.

ABSTRACT: γδT cells hold a pivotal role in tumor immunosurveillance through their prompt activation and cytokine secretion, their ability to kill tumor cells in an Human Leukocyte Antigen (HLA)-unrestricted manner, and their combination of features of both innate and adaptive immunity. These unique properties and functional plasticity render them very attractive both as targets and vectors for cancer immunotherapy. Yet, these potent and fascinating antitumor effectors have not been extensively explored in melanoma. We provided here a detailed investigation of the phenotypic and functional properties of circulating and tumor-infiltrating γδT cells in melanoma patients, and their impact on clinical evolution. High proportions of circulating- and tumor-infiltrating γδT and δ2+ subset were associated with better clinical outcome. We reported however that circulating and tumor-infiltrating γδT cells from melanoma patients displayed an altered expression of NCR, KIR, and immune checkpoints, and identified NKp44, PD1, 41BB/41BBL, TIM3, and LAG3 as crucial checkpoints allowing immune escape and tumor progression. Notably, melanoma drastically impaired the ability of γδT cells to exhibit activation molecules, secrete cytokines, and display cytotoxicity toward melanoma in response to stimulation with phosphoantigens. It drove them toward regulatory and Th17 profiles associated with poor clinical outcomes. Our study highlights that melanoma hijacked γδT cells to escape from immune control, and revealed that circulating and tumor-infiltrating γδT cell features are promising potential biomarkers of clinical evolution. Such understanding of the physiopathology of γδT cells may help designing new therapeutic approaches exploiting the antitumor potential of γδT cells while counteracting their skewing by tumors to improve patient outcomes.

5 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.

6 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.

7 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.

8 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.

9 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.