Restoring tumor immunogenicity with dendritic cell reprogramming

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Restoring tumor immunogenicity with dendritic cell reprogramming. / Zimmermannova, Olga; Ferreira, Alexandra G.; Ascic, Ervin; Santiago, Marta Velasco; Kurochkin, Ilia; Hansen, Morten; Met, Özcan; Caiado, Inês; Shapiro, Ilja E.; Michaux, Justine; Humbert, Marion; Soto-Cabrera, Diego; Benonisson, Hreinn; Silvério-Alves, Rita; Gomez-Jimenez, David; Bernardo, Carina; Bauden, Monika; Andersson, Roland; Höglund, Mattias; Miharada, Kenichi; Nakamura, Yukio; Hugues, Stephanie; Greiff, Lennart; Lindstedt, Malin; Rosa, Fábio F.; Pires, Cristiana F.; Bassani-Sternberg, Michal; Svane, Inge Marie; Pereira, Carlos Filipe.

In: Science immunology, Vol. 8, No. 85, eadd4817, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zimmermannova, O, Ferreira, AG, Ascic, E, Santiago, MV, Kurochkin, I, Hansen, M, Met, Ö, Caiado, I, Shapiro, IE, Michaux, J, Humbert, M, Soto-Cabrera, D, Benonisson, H, Silvério-Alves, R, Gomez-Jimenez, D, Bernardo, C, Bauden, M, Andersson, R, Höglund, M, Miharada, K, Nakamura, Y, Hugues, S, Greiff, L, Lindstedt, M, Rosa, FF, Pires, CF, Bassani-Sternberg, M, Svane, IM & Pereira, CF 2023, 'Restoring tumor immunogenicity with dendritic cell reprogramming', Science immunology, vol. 8, no. 85, eadd4817. https://doi.org/10.1126/sciimmunol.add4817

APA

Zimmermannova, O., Ferreira, A. G., Ascic, E., Santiago, M. V., Kurochkin, I., Hansen, M., Met, Ö., Caiado, I., Shapiro, I. E., Michaux, J., Humbert, M., Soto-Cabrera, D., Benonisson, H., Silvério-Alves, R., Gomez-Jimenez, D., Bernardo, C., Bauden, M., Andersson, R., Höglund, M., ... Pereira, C. F. (2023). Restoring tumor immunogenicity with dendritic cell reprogramming. Science immunology, 8(85), [eadd4817]. https://doi.org/10.1126/sciimmunol.add4817

Vancouver

Zimmermannova O, Ferreira AG, Ascic E, Santiago MV, Kurochkin I, Hansen M et al. Restoring tumor immunogenicity with dendritic cell reprogramming. Science immunology. 2023;8(85). eadd4817. https://doi.org/10.1126/sciimmunol.add4817

Author

Zimmermannova, Olga ; Ferreira, Alexandra G. ; Ascic, Ervin ; Santiago, Marta Velasco ; Kurochkin, Ilia ; Hansen, Morten ; Met, Özcan ; Caiado, Inês ; Shapiro, Ilja E. ; Michaux, Justine ; Humbert, Marion ; Soto-Cabrera, Diego ; Benonisson, Hreinn ; Silvério-Alves, Rita ; Gomez-Jimenez, David ; Bernardo, Carina ; Bauden, Monika ; Andersson, Roland ; Höglund, Mattias ; Miharada, Kenichi ; Nakamura, Yukio ; Hugues, Stephanie ; Greiff, Lennart ; Lindstedt, Malin ; Rosa, Fábio F. ; Pires, Cristiana F. ; Bassani-Sternberg, Michal ; Svane, Inge Marie ; Pereira, Carlos Filipe. / Restoring tumor immunogenicity with dendritic cell reprogramming. In: Science immunology. 2023 ; Vol. 8, No. 85.

Bibtex

@article{004eee7ef1d2496aa886ca01384cd88c,

title = "Restoring tumor immunogenicity with dendritic cell reprogramming",

abstract = "Decreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen-presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce the cDC1 phenotype in 36 cell lines derived from human and mouse hematological and solid tumors.Within 9 days of reprogramming, tumor-APCs acquired transcriptional and epigenetic programs associated with cDC1 cells. Reprogramming restored the expression of antigen presentation complexes and costimulatory molecules on the surfaces of tumor cells, allowing the presentation of endogenous tumor antigens on MHC-I and facilitating targeted killing by CD8+ T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross-presented antigens to na{\"i}ve CD8+ T cells. Human primary tumor cells could also be reprogrammed to increase their capability to present antigen and to activate patient-specific tumor-infiltrating lymphocytes. In addition to acquiring improved antigen presentation, tumor-APCs had impaired tumorigenicity in vitro and in vivo. Injection of in vitro generated melanoma-derived tumor-APCs into subcutaneous melanoma tumors delayed tumor growth and increased survival in mice. Antitumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors. Our approach serves as a platform for the development of immunotherapies that endow cancer cells with the capability to process and present endogenous tumor antigens. ",

author = "Olga Zimmermannova and Ferreira, {Alexandra G.} and Ervin Ascic and Santiago, {Marta Velasco} and Ilia Kurochkin and Morten Hansen and {\"O}zcan Met and In{\^e}s Caiado and Shapiro, {Ilja E.} and Justine Michaux and Marion Humbert and Diego Soto-Cabrera and Hreinn Benonisson and Rita Silv{\'e}rio-Alves and David Gomez-Jimenez and Carina Bernardo and Monika Bauden and Roland Andersson and Mattias H{\"o}glund and Kenichi Miharada and Yukio Nakamura and Stephanie Hugues and Lennart Greiff and Malin Lindstedt and Rosa, {F{\'a}bio F.} and Pires, {Cristiana F.} and Michal Bassani-Sternberg and Svane, {Inge Marie} and Pereira, {Carlos Filipe}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors.",

year = "2023",

doi = "10.1126/sciimmunol.add4817",

language = "English",

volume = "8",

journal = "Advances in Immunology",

issn = "0065-2776",

publisher = "American Association for the Advancement of Science",

number = "85",

}

RIS

TY - JOUR

T1 - Restoring tumor immunogenicity with dendritic cell reprogramming

AU - Zimmermannova, Olga

AU - Ferreira, Alexandra G.

AU - Ascic, Ervin

AU - Santiago, Marta Velasco

AU - Kurochkin, Ilia

AU - Hansen, Morten

AU - Met, Özcan

AU - Caiado, Inês

AU - Shapiro, Ilja E.

AU - Michaux, Justine

AU - Humbert, Marion

AU - Soto-Cabrera, Diego

AU - Benonisson, Hreinn

AU - Silvério-Alves, Rita

AU - Gomez-Jimenez, David

AU - Bernardo, Carina

AU - Bauden, Monika

AU - Andersson, Roland

AU - Höglund, Mattias

AU - Miharada, Kenichi

AU - Nakamura, Yukio

AU - Hugues, Stephanie

AU - Greiff, Lennart

AU - Lindstedt, Malin

AU - Rosa, Fábio F.

AU - Pires, Cristiana F.

AU - Bassani-Sternberg, Michal

AU - Svane, Inge Marie

AU - Pereira, Carlos Filipe

PY - 2023

Y1 - 2023

N2 - Decreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen-presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce the cDC1 phenotype in 36 cell lines derived from human and mouse hematological and solid tumors.Within 9 days of reprogramming, tumor-APCs acquired transcriptional and epigenetic programs associated with cDC1 cells. Reprogramming restored the expression of antigen presentation complexes and costimulatory molecules on the surfaces of tumor cells, allowing the presentation of endogenous tumor antigens on MHC-I and facilitating targeted killing by CD8+ T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross-presented antigens to naïve CD8+ T cells. Human primary tumor cells could also be reprogrammed to increase their capability to present antigen and to activate patient-specific tumor-infiltrating lymphocytes. In addition to acquiring improved antigen presentation, tumor-APCs had impaired tumorigenicity in vitro and in vivo. Injection of in vitro generated melanoma-derived tumor-APCs into subcutaneous melanoma tumors delayed tumor growth and increased survival in mice. Antitumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors. Our approach serves as a platform for the development of immunotherapies that endow cancer cells with the capability to process and present endogenous tumor antigens.

AB - Decreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen-presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce the cDC1 phenotype in 36 cell lines derived from human and mouse hematological and solid tumors.Within 9 days of reprogramming, tumor-APCs acquired transcriptional and epigenetic programs associated with cDC1 cells. Reprogramming restored the expression of antigen presentation complexes and costimulatory molecules on the surfaces of tumor cells, allowing the presentation of endogenous tumor antigens on MHC-I and facilitating targeted killing by CD8+ T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross-presented antigens to naïve CD8+ T cells. Human primary tumor cells could also be reprogrammed to increase their capability to present antigen and to activate patient-specific tumor-infiltrating lymphocytes. In addition to acquiring improved antigen presentation, tumor-APCs had impaired tumorigenicity in vitro and in vivo. Injection of in vitro generated melanoma-derived tumor-APCs into subcutaneous melanoma tumors delayed tumor growth and increased survival in mice. Antitumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors. Our approach serves as a platform for the development of immunotherapies that endow cancer cells with the capability to process and present endogenous tumor antigens.

U2 - 10.1126/sciimmunol.add4817

DO - 10.1126/sciimmunol.add4817

M3 - Journal article

C2 - 37418548

AN - SCOPUS:85164260695

VL - 8

JO - Advances in Immunology

JF - Advances in Immunology

SN - 0065-2776

IS - 85

M1 - eadd4817

ER -

ID: 370733375