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.
journal_name
Pigment Cell Melanoma Resjournal_title
Pigment cell & melanoma researchauthors
Charles J,Chaperot L,Revol B,Baudin M,Mouret S,Hamon A,Leccia MT,Plumas J,Aspord Cdoi
10.1111/pcmr.12618subject
Has Abstractpub_date
2018-01-01 00:00:00pages
82-94issue
1eissn
1755-1471issn
1755-148Xjournal_volume
31pub_type
杂志文章abstract::Normal cells possess a limited proliferative life span, after which they enter a state of irreversible growth arrest, called replicative senescence, which acts as a potent barrier against transformation. Transformed cells have escaped the process of replicative senescence and theoretically can not re-enter senescence....
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2010.00820.x
更新日期:2011-04-01 00:00:00
abstract::A SNP within intron4 of the interferon regulatory factor4 (IRF4) gene, rs12203592*C/T, has been independently associated with pigmentation and age-specific effects on naevus count in European-derived populations. We have characterized the cis-regulatory activity of this intronic region and using human foreskin-derived...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12620
更新日期:2018-01-01 00:00:00
abstract::Hair color and skin color are frequently coordinated in mammalian species. To explore this, we have studied mutations in two different G protein coupled pathways, each of which affects the darkness of both hair and skin color. In each mouse mutant (Gnaq(Dsk1), Gna11(Dsk7), and Mc1r(e)), we analyzed the melanocyte dens...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2009.00609.x
更新日期:2009-12-01 00:00:00
abstract::Although L-tyrosine is well known for its melanogenic effect, the contribution of D-tyrosine to melanin synthesis was previously unexplored. Here, we reveal that, unlike L-tyrosine, D-tyrosine dose-dependently reduced the melanin contents of human MNT-1 melanoma cells and primary human melanocytes. In addition, 500 μM...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12668
更新日期:2018-05-01 00:00:00
abstract::We have recently reported that human melanoma cells express a variety of voltage-gated calcium (Ca(2+) ) channel types, including low-voltage-activated T-type channels that play a significant role in melanoma cell cycle progression. Here, we challenged melanoma metastatic cells with T-type channel blockers of clinical...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12155
更新日期:2013-11-01 00:00:00
abstract::Retinoic acid (RA) is considered to control melanocytes; however, its precise mechanism remains unclear because of a bimodal effect, which promotes or inhibits melanin synthesis depending on the cell type, culture condition of melanocytes and skin conditions. In this study, we examined the effects of RA throughout eac...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2012.00988.x
更新日期:2012-05-01 00:00:00
abstract::Genome-wide association studies (GWAS) have become a widely used approach for genetic association studies of various human traits. A few GWAS have been conducted with the goal of identifying novel loci for pigmentation traits, melanoma, and non-melanoma skin cancer. Nevertheless, the phenotype variation explained by t...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2012.01023.x
更新日期:2012-09-01 00:00:00
abstract::Oncogenic BRAF and NRAS mutations drive human melanoma initiation. We used transgenic zebrafish to model NRAS-mutant melanoma, and the rapid tumor onset allowed us to study candidate tumor suppressors. We identified P38α-MAPK14 as a potential tumor suppressor in The Cancer Genome Atlas melanoma cohort of NRAS-mutant m...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12925
更新日期:2020-09-10 00:00:00
abstract::We investigated the contributions of Tyrp1 and Gpnmb to the iris transillumination defect (TID) in five age cohorts of BXD mice. Using systems genetics, we also evaluated the role of other known pigmentation genes (PGs). Mapping studies indicate that Tyrp1 contributes to the phenotype at all ages, yet the TID maps to ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12106
更新日期:2013-07-01 00:00:00
abstract::The tricarboxylic acid (TCA) cycle is the central hub of oxidative metabolism, running in the classic forward direction to provide carbon for biosynthesis and reducing agents for generation of ATP. Our metabolic tracer studies in melanoma cells showed that in hypoxic conditions the TCA cycle is largely disconnected fr...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2012.00989.x
更新日期:2012-05-01 00:00:00
abstract::Melanoma is a disease associated with a very high mutation burden and thus the possibility of a diverse range of oncogenic mechanisms that allow it to evade therapeutic interventions and the immune system. Here, we describe the characterization of a panel of 102 cell lines from metastatic melanomas (the NZM lines), in...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12908
更新日期:2021-01-01 00:00:00
abstract::The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas - dia...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12475
更新日期:2016-07-01 00:00:00
abstract::The aim of present study was to evaluate CD4(+) /CD8(+) ratio and CD4(+) CD25(hi) FoxP3(+) Tregs in GV patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4(+) /CD8(+) ratio and Tregs in 82 patients and 50 controls. CD8(+) T-cell counts were signific...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12105
更新日期:2013-07-01 00:00:00
abstract::The presence of melanin pigment within the iris is responsible for the visual impression of human eye colouration with complex patterns also evident in this tissue, including Fuchs' crypts, nevi, Wolfflin nodules and contraction furrows. The genetic basis underlying the determination and inheritance of these traits ha...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2009.00606.x
更新日期:2009-10-01 00:00:00
abstract::Evidence on the relationship between the vitamin D pathway and outcomes in melanoma is growing, although it is not always clear. We investigated the impact of measured levels of sun exposure at diagnosis on associations of vitamin D receptor gene (VDR) polymorphisms and melanoma death in 3336 incident primary melanoma...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12653
更新日期:2018-03-01 00:00:00
abstract::The complex genetic changes underlying metastatic melanoma need to be deciphered to develop new and effective therapeutics. Previously, genome-wide microarray analyses of human melanoma identified two reciprocal gene expression programs, including transcripts regulated by either transforming growth factor, beta 1 (TGF...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12255
更新日期:2014-09-01 00:00:00
abstract::Mice lacking the E3 ubiquitin ligase mahogunin ring finger-1 (MGRN1) have a pleiotropic phenotype that includes spongiform neurodegeneration, embryonic patterning defects, and dark fur due to a defect in pigment-type switching. The only MGRN1 ubiquitination target identified to date is tumor susceptibility gene 101 (T...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12059
更新日期:2013-03-01 00:00:00
abstract::Some familial forms of the dermatological condition vitiligo have recently been linked to polymorphisms in the innate immunity gene, NLRP1. Here, we review what is currently known about the mechanisms that regulate activation of the NLRP1 protein and the downstream effects of NLRP1 on pathways impacting inflammation a...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2011.00942.x
更新日期:2012-01-01 00:00:00
abstract::Microphthalmia-associated transcription factor (MITF) is a survival factor in melanocytes and melanoma cells. MITF regulates expression of antiapoptotic genes and promotes lineage-specific survival in response to ultraviolet (UV) radiation and to chemotherapeutics. SWI/SNF chromatin-remodeling enzymes interact with MI...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12088
更新日期:2013-05-01 00:00:00
abstract::One of the main advantages of using inducible and conditional transgenes to study pigment cell biology is that they allow for genetic manipulation within melanocytes after roles in general neural crest or melanoblast development have been fulfilled. Specifically, we focus here on the ability of the Tyr::CreER(T) ...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12048
更新日期:2013-03-01 00:00:00
abstract::Metastatic melanoma is extremely refractory to existing chemotherapeutic drugs and bioimmune adjuvant therapies, and the life span of patients with metastatic melanoma is often measured in months. Understanding the mechanisms responsible for the development of tumor metastasis is critical for finding successful curati...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2009.00570.x
更新日期:2009-06-01 00:00:00
abstract::Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults. With over 50% of patients developing metastatic disease, there is an unmet need for improved diagnostic and therapeutic options. Efforts to understand the molecular biology of the disease have revealed several markers that correlate with...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12810
更新日期:2020-01-01 00:00:00
abstract::Zebrafish respond to visual stimuli to adapt their body colour to the background. If, rather than being a simple on/off reaction to visual stimulation, the colour change involves cognitive and memory-related processes, training fish with cyclical changes of the background would be expected to increase its ability to c...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/j.1755-148X.2008.00445.x
更新日期:2008-06-01 00:00:00
abstract::Bromodomain and extra-terminal inhibitors (BETi) delay tumor growth, in part, through tumor cell intrinsic alterations and initiation of anti-tumor CD8+ T-cell responses. By contrast, BETi effects on pro-tumoral immune responses remain unclear. Here, we show that the next-generation BETi, PLX51107, delayed tumor growt...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12845
更新日期:2020-03-01 00:00:00
abstract::Hermansky-Pudlak syndrome (HPS) is a rare recessive disorder characterized by hypopigmentation, bleeding diathesis, and other symptoms due to multiple defects in lysosome-related organelles. Ten HPS subtypes have been identified with mutations in HPS1 to HPS10. Only four patients with HPS-1 have been reported in Chine...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12534
更新日期:2016-11-01 00:00:00
abstract::The liver is the organ usually affected by metastatic uveal melanoma (MUM). Current treatments are almost always ineffective and mortality remains high. In this study, copy number variations (CNVs) were identified in 12 metastatic and five matched primary UMs (PUMs). Our data revealed a wide spectrum of genetic altera...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12433
更新日期:2016-01-01 00:00:00
abstract::In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System Metastases in Tampa, Florida. The meeting included investigators from multiple academic centers and disciplines. A consensus summary of the progress and challenges in melanoma pa...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/pcmr.12861
更新日期:2020-07-01 00:00:00
abstract::While sunlight is important for life, ultraviolet radiation (UVR) can have harmful and mutagenic effects. This duality is particularly relevant to human skin, in which UVR both participates in evolutionarily important photochemical reactions yet may act as a potential carcinogen. UVR can upregulate production of melan...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章,评审
doi:10.1111/j.1755-148X.2010.00775.x
更新日期:2010-12-01 00:00:00
abstract::Monobenzone is a 4-substituted phenol that can induce vitiligo and antimelanoma immunity. We investigated the influence of the chemical structure on the biological activity of a series of structurally related 4-substituted phenols. All phenols inhibited cellular melanin synthesis, and eight of ten phenols inhibited ty...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12774
更新日期:2019-07-01 00:00:00
abstract::Induced pluripotent stem cell (iPSC) technology offers a novel approach for conversion of human primary fibroblasts into melanocytes. During attempts to explore various protocols for differentiation of iPSCs into melanocytes, we found a distinct and self-renewing cell lineage that could differentiate into melanocytes,...
journal_title:Pigment cell & melanoma research
pub_type: 杂志文章
doi:10.1111/pcmr.12779
更新日期:2019-09-01 00:00:00