The CD4+ T-Cell Response of Melanoma Patients to a MAGE-A3 Peptide Vaccine Involves Potential Regulatory T Cells

François, Violaine; Ottaviani, Sabrina; Renkvist, Nicolina; Stockis, Julie; Thielemans, Kris; Colau, Didier; Marchand, Marie; Boon, Thierry; Lucas, Sophie; Bruggen, Pierre van der

doi:10.1158/0008-5472.can-08-3726

Cited by 82 publications

(61 citation statements)

References 49 publications

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“…This is surprising given the low amounts of IL-12p70 released from cocktailmatured DC in vitro but may be explained by their expression of CD70 [20,54]. The vaccine-specific Th cells were FOXP3-negative, indicating that vaccine-specific natural Treg were not induced, which is counterintuitive to a previous report [55], yet compatible with recent Treg cloning data [56]. Vaccine-specific CTL were, however, only weakly detectable ex vivo, but the CTLp frequency was markedly increased, and many CTL were of high affinity.…”

Section: Modc As a Focus For Comparisonsupporting

confidence: 52%

Dendritic cells in cancer immunotherapy

Schuler

2010

Eur J Immunol

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DC initiate and regulate T‐cell immunity and are thus the key to optimization of all types of vaccines. Insights into DC biology offer many opportunities to enhance immunogenicity. In this Viewpoint, I discuss some recent developments and findings that are of immediate relevance for the clinical development of cancer vaccines. In addition, I emphasize my personal view that we should explore the potential of adoptively transferred DC (i.e. DC vaccination) as cancer vaccines by performing two‐armed trials that address critical variables and by delivering antigens via mRNA‐transfected DC.

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Section: Modc As a Focus For Comparisonsupporting

confidence: 52%

Dendritic cells in cancer immunotherapy

Schuler

2010

Eur J Immunol

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“…In mice, it has been reported that the expansion of iTregs upon vaccination dampens antitumor Th1 responses [87]. In human, the group of Peter Van der Bruggen has demonstrated that the CD4 + T-cell response of melanoma patients to a MAGE-A3-derived peptide vaccine involves regulatory T cells [88]. In individuals vaccinated with E6/E7-derived long peptides, immunosuppressive cells has been shown to expand [89], correlating to the development of resistance against an anti-HPV therapeutic vaccine [90].…”

Section: Specificity Of Tregsmentioning

confidence: 99%

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Tanchot

Terme

Péré

et al. 2012

Cancer Microenvironment

115

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In immunocompetent individuals, the immune system initially eradicates potentially tumorigenic cells as they develop, a capacity that is progressively lost when malignant cells acquire alterations that sustain immunosubversion and/or immunoevasion. One of the major mechanisms whereby cancer cells block antitumor immune responses involves a specific class of immunosuppressive T cells that-in the vast majority of cases-express the Forkhead box P3 (FOXP3) transcription factor. Such FOXP3 + regulatory T cells (Tregs) accumulate within neoplastic lesions as a result of several distinct mechanisms, including increased infiltration, local expansion, survival advantage and in situ development from conventional CD4 + cells.

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“…Most recently, the Wilm's TA overexpressed by leukemias was shown to stimulate TA-specific Treg clones generated in vitro from PBLs of normal donors (14). In addition, immunization with one MAGE-A3 peptide resulted in induction of TA-specific regulatory T cells isolated from PBLs of vaccinated melanoma patients (15).…”

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confidence: 99%

Human Tumor Antigen-Specific Helper and Regulatory T Cells Share Common Epitope Specificity but Exhibit Distinct T Cell Repertoire

Fourcade¹,

Sun²,

Kudela³

et al. 2010

The Journal of Immunology

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CD4+ regulatory T cells (Tregs) accumulate at tumor sites and play a critical role in the suppression of immune responses against tumor cells. In this study, we show that two immunodominant epitopes derived from the tumor Ags (TAs) NY-ESO-1 and TRAG-3 stimulate both CD4+ Th cells and Tregs. TA-specific Tregs inhibit the proliferation of allogenic T cells, act in a cell-to-cell contact dependent fashion and require activation to suppress IL-2 secretion by T cells. TRAG-3 and NY-ESO-1–specific Tregs exhibit either a Th1-, a Th2-, or a Th0-type cytokine profile and dot not produce IL-10 or TGF-β. The Foxp3 levels vary from one Treg clone to another and are significantly lower than those of CD4+CD25high Tregs. In contrast to NY-ESO-1–specific Th cells, the NY-ESO-1–specific and TRAG-3–specific Treg clonotypes share a common TCR CDR3 Vβ usage with Foxp3+CD4+CD25high and CD4+CD25− T cells and were not detectable in PBLs of other melanoma patients and of healthy donors, suggesting that their recruitment occurs through the peripheral conversion of CD4+CD25− T cells upon chronic Ag exposure. Collectively, our findings demonstrate that the same epitopes spontaneously stimulate both Th cells and Tregs in patients with advanced melanoma. They also suggest that TA-specific Treg expansion may be better impaired by therapies aimed at depleting CD4+CD25high Tregs and preventing the peripheral conversion of CD4+CD25− T cells.

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The CD4+ T-Cell Response of Melanoma Patients to a MAGE-A3 Peptide Vaccine Involves Potential Regulatory T Cells

Cited by 82 publications

References 49 publications

Dendritic cells in cancer immunotherapy

Dendritic cells in cancer immunotherapy

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Human Tumor Antigen-Specific Helper and Regulatory T Cells Share Common Epitope Specificity but Exhibit Distinct T Cell Repertoire

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