Presentation is loading. Please wait.

Presentation is loading. Please wait.

HLA-A*0201+ Plasmacytoid Dendritic Cells Provide a Cell-Based Immunotherapy for Melanoma Patients  Caroline Aspord, Marie-Therese Leccia, Dimitri Salameire,

Published byIngar Iversen Modified over 6 years ago

Similar presentations

Presentation on theme: "HLA-A*0201+ Plasmacytoid Dendritic Cells Provide a Cell-Based Immunotherapy for Melanoma Patients  Caroline Aspord, Marie-Therese Leccia, Dimitri Salameire,"— Presentation transcript:

1 HLA-A*0201+ Plasmacytoid Dendritic Cells Provide a Cell-Based Immunotherapy for Melanoma Patients 
Caroline Aspord, Marie-Therese Leccia, Dimitri Salameire, David Laurin, Laurence Chaperot, Julie Charles, Joel Plumas  Journal of Investigative Dermatology  Volume 132, Issue 10, Pages (October 2012) DOI: /jid Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 The HLA-A*0201+ plasmacytoid dendritic cell (pDC) line loaded with melanoma-derived peptides induces multi-specific T-cell responses ex vivo from peripheral blood mononuclear cells (PBMCs) from stage I–IV melanoma patients. PBMCs obtained from stage I–IV HLA-A*0201+ melanoma patients (n=16) were cocultured with irradiated pDCs loaded with (a, c) one or (b, c) a mixture (mix) of peptides from among MelA-, gp100-, tyrosinase-, and MAGE-A3-derived HLA-A*0201-restricted peptides. Cultures were restimulated weekly in the presence of IL2. T cells were tetramer labeled at days 0, 7, 14, and 20 of culture to determine the percentage of specific cells. (a, b) Representative dotplots for each tumor antigen (gated on CD8+ T cells). (c) Percentages of tumor-specific T cells obtained initially and at different culture time points for 16 patients. d, day. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 The HLA-A*0201+ plasmacytoid dendritic cell (pDC) line loaded with melanoma-derived peptides induces multi-specific T-cell responses ex vivo from tumor-infiltrating lymphocytes (TILs) from stage III to IV melanoma patients. TILs obtained from stage III to IV HLA-A*0201+ melanoma patients (n=17) were cocultured with irradiated pDCs loaded with (a, c) one or (b, c) a mixture (mix) of peptides from among MelA-, gp100-, tyrosinase-, and MAGE-A3-derived HLA-A*0201-restricted peptides. Cultures were restimulated weekly in the presence of IL2. T cells were tetramer-labeled at days 0, 7, 14, and 20 of culture to determine the percentage of specific cells. (a, b) Representative dotplots for each tumor antigen (gated on CD8+ T cells). (c) Percentages of tumor-specific T cells at different culture time points for 18 patients. d, day. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 Melanoma patients’ response to the plasmacytoid dendritic cell (pDC) strategy and immune score. (a) Percentage of patients responding to the pDC stimulation for each tumor antigen (16 peripheral blood mononuclear cell (PBMC), 18 tumor-infiltrating lymphocytes (TIL)). (b) An immune score was defined based on the patients’ ability to respond to one (score 1), two (score 2), three (score 3), or four (score 4) antigens. Percentage of patients for each score, after stimulation with pDCs loaded with either a single peptide or the four-peptide mixture (16 PBMC, 18 TIL). Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 Tumor-specific T cells primed by peptide-loaded plasmacytoid dendritic cells (pDCs) secrete IFNγ and express CD107 on the surface upon specific restimulation. (a, b) Peripheral blood mononuclear cells (PBMCs) or (c–f) tumor-infiltrating lymphocytes (TILs) were cocultured with irradiated pDCs loaded with a single peptide or a mixture of the MelA-, GP100-, tyrosinase-, and MAGE-A3-derived HLA-A*0201-restricted peptides and restimulated weekly in the presence of IL2. Cells were tetramer labeled and restimulated with T2 cells pulsed with a relevant or control peptide. (a–d) IFNγ production was assessed by intracellular staining. CD107 expression was evaluated by adding anti-CD107a+b antibodies during restimulation. (a, c, e) Representative dotplots gated on CD8+ T cells (left panels) and tetramer+ CD8+ T cells (right panels). (b, d) Percent IFNγ+ tumor-specific T cells. (f) Percent CD107+ tumor-specific T cells. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

6 Figure 5 Tumor-specific T cells elicited by plasmacytoid dendritic cells (pDCs) from melanoma patients’ peripheral blood mononuclear cells (PBMCs) are highly cytotoxic. T cells induced from melanoma patients’ PBMCs by peptide-loaded pDCs were purified and used as effectors in a 51Cr-release assay. (a) Representative cytotoxicity assays on peptide-loaded T2 cells upon stimulation with single peptide–loaded pDCs. (b) Representative cytotoxicity assays on allogeneic melanoma tumor cells upon stimulation with pDCs loaded with MelA (left panel) or the four-peptide mixture (mix; right panel). (c) Killing of peptide-loaded T2 cells obtained with T cells specific to the corresponding peptide (left, single peptide, n=23; right, four-peptide mix, n=15). (d) Killing of allogeneic melanoma tumor cells obtained with PBMCs after stimulation with pDCs loaded with the four-peptide mixture; patients responding to tyrosinase were excluded (n=11). Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

7 Figure 6 Tumor-specific T cells elicited by plasmacytoid dendritic cells (pDCs) from melanoma patients’ tumor-infiltrating lymphocytes (TILs) are highly cytotoxic and lyse autologous melanoma tumor cells. Unstimulated TILs (TIL day (d)0) or T cells induced from TILs by peptide-loaded pDCs were used as effectors in a 51Cr-release assay. (a) Representative cytotoxicity toward peptide-loaded T2 cells obtained with TILs responding to the antigens indicated. Representative cytotoxicity assays on (b, d) allogeneic or (c, e) autologous melanoma cells obtained with unstimulated TILs or TILs stimulated with pDCs loaded with (b, c) a single peptide or (d, e) the four-peptide mixture. (f) Percentage of cytotoxicity toward allogeneic (upper panels) or autologous melanoma cells and corresponding CD45+ cells (lower panels) obtained with unstimulated TILs or TILs stimulated with pDCs loaded with a single peptide or the four-peptide mixture. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

8 Figure 6 Tumor-specific T cells elicited by plasmacytoid dendritic cells (pDCs) from melanoma patients’ tumor-infiltrating lymphocytes (TILs) are highly cytotoxic and lyse autologous melanoma tumor cells. Unstimulated TILs (TIL day (d)0) or T cells induced from TILs by peptide-loaded pDCs were used as effectors in a 51Cr-release assay. (a) Representative cytotoxicity toward peptide-loaded T2 cells obtained with TILs responding to the antigens indicated. Representative cytotoxicity assays on (b, d) allogeneic or (c, e) autologous melanoma cells obtained with unstimulated TILs or TILs stimulated with pDCs loaded with (b, c) a single peptide or (d, e) the four-peptide mixture. (f) Percentage of cytotoxicity toward allogeneic (upper panels) or autologous melanoma cells and corresponding CD45+ cells (lower panels) obtained with unstimulated TILs or TILs stimulated with pDCs loaded with a single peptide or the four-peptide mixture. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

Download ppt "HLA-A*0201+ Plasmacytoid Dendritic Cells Provide a Cell-Based Immunotherapy for Melanoma Patients  Caroline Aspord, Marie-Therese Leccia, Dimitri Salameire,"

Similar presentations

Supplementary Figure 3 Antigen-specific responses are enhanced by stimulation in an in vitro stimulation (IVS) assay, as well as with stimulation using.

Supplementary Figure 3 Antigen-specific responses are enhanced by stimulation in an in vitro stimulation (IVS) assay, as well as with stimulation using.
Prevention and Mitigation of Experimental Autoimmune Encephalomyelitis by Murine β- Defensins via Induction of Regulatory T Cells  Anika Bruhs, Thomas.

Prevention and Mitigation of Experimental Autoimmune Encephalomyelitis by Murine β- Defensins via Induction of Regulatory T Cells  Anika Bruhs, Thomas.
Volume 19, Issue 12, Pages (December 2011)

Volume 19, Issue 12, Pages (December 2011)
A Promiscuous Survivin-Derived T-Cell Epitope Restricted to the HLA-A3 Super-Type Alleles  Niels Junker, Shamaila Munir, Pia Kvistborg, Per thor Straten,

A Promiscuous Survivin-Derived T-Cell Epitope Restricted to the HLA-A3 Super-Type Alleles  Niels Junker, Shamaila Munir, Pia Kvistborg, Per thor Straten,
Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses by Giulia Nizzoli, Jana Krietsch, Anja Weick, Svenja.

Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses by Giulia Nizzoli, Jana Krietsch, Anja Weick, Svenja.
CD271 on Melanoma Cell Is an IFN-γ-Inducible Immunosuppressive Factor that Mediates Downregulation of Melanoma Antigens  Junpei Furuta, Takashi Inozume,

CD271 on Melanoma Cell Is an IFN-γ-Inducible Immunosuppressive Factor that Mediates Downregulation of Melanoma Antigens  Junpei Furuta, Takashi Inozume,
Non-small Cell Lung Cancer Induces an Immunosuppressive Phenotype of Dendritic Cells in Tumor Microenvironment by Upregulating B7-H3  Thomas Schneider,

Non-small Cell Lung Cancer Induces an Immunosuppressive Phenotype of Dendritic Cells in Tumor Microenvironment by Upregulating B7-H3  Thomas Schneider,
Antigen-Specific CD8 T Cells Can Eliminate Antigen-Bearing Keratinocytes with Clonogenic Potential via an IFN-γ-Dependent Mechanism  Rachel L. De Kluyver,

Antigen-Specific CD8 T Cells Can Eliminate Antigen-Bearing Keratinocytes with Clonogenic Potential via an IFN-γ-Dependent Mechanism  Rachel L. De Kluyver,
IL-21 May Promote Granzyme B-Dependent NK/Plasmacytoid Dendritic Cell Functional Interaction in Cutaneous Lupus Erythematosus  Valentina Salvi, William.

IL-21 May Promote Granzyme B-Dependent NK/Plasmacytoid Dendritic Cell Functional Interaction in Cutaneous Lupus Erythematosus  Valentina Salvi, William.
Impaired Responses of Peripheral Blood Mononuclear Cells to Staphylococcal Superantigen in Patients with Severe Atopic Dermatitis: A Role of T Cell Apoptosis 

Impaired Responses of Peripheral Blood Mononuclear Cells to Staphylococcal Superantigen in Patients with Severe Atopic Dermatitis: A Role of T Cell Apoptosis 
Volume 31, Issue 5, Pages (November 2009)

Volume 31, Issue 5, Pages (November 2009)
Dissolving Microneedle Delivery of Nanoparticle-Encapsulated Antigen Elicits Efficient Cross-Priming and Th1 Immune Responses by Murine Langerhans Cells 

Dissolving Microneedle Delivery of Nanoparticle-Encapsulated Antigen Elicits Efficient Cross-Priming and Th1 Immune Responses by Murine Langerhans Cells 
Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants by Georg.

Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants by Georg.
Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients by Devi.

Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients by Devi.
Mature dendritic cells pulsed with freeze–thaw cell lysates define an effective in vitro vaccine designed to elicit EBV-specific CD4+ and CD8+ T lymphocyte.

Mature dendritic cells pulsed with freeze–thaw cell lysates define an effective in vitro vaccine designed to elicit EBV-specific CD4+ and CD8+ T lymphocyte.
Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients by Raffaella.

Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients by Raffaella.
Cord Blood CD34+ Cells Differentiate into Dermal Dendritic Cells in Co-Culture with Cutaneous Fibroblasts or Stromal Cells  Zia U.A. Mollah, Setsuya Aiba,

Cord Blood CD34+ Cells Differentiate into Dermal Dendritic Cells in Co-Culture with Cutaneous Fibroblasts or Stromal Cells  Zia U.A. Mollah, Setsuya Aiba,
Methods to Improve Adoptive T-Cell Therapy for Melanoma: IFN-γ Enhances Anticancer Responses of Cell Products for Infusion  Marco Donia, Morten Hansen,

Methods to Improve Adoptive T-Cell Therapy for Melanoma: IFN-γ Enhances Anticancer Responses of Cell Products for Infusion  Marco Donia, Morten Hansen,
Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell–depleted stem cell transplantation.

Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell–depleted stem cell transplantation.
Alternative Activation of Human Plasmacytoid DCs In Vitro and in Melanoma Lesions: Involvement of LAG-3  Chiara Camisaschi, Annamaria De Filippo, Valeria.

Alternative Activation of Human Plasmacytoid DCs In Vitro and in Melanoma Lesions: Involvement of LAG-3  Chiara Camisaschi, Annamaria De Filippo, Valeria.

Similar presentations

Ads by Google