In vivo dendritic cell reprogramming for cancer immunotherapy

Ervin Ascic; Fritiof Åkerström; Malavika Sreekumar Nair; André Rosa; Ilia Kurochkin; Olga Zimmermannova; Xavier Catena; Nadezhda Rotankova; Charlotte Veser; Michal Rudnik; Tommaso Ballocci; Tiffany Schärer; Xiaoli Huang; Maria de Rosa Torres; Emilie Renaud; Marta Velasco Santiago; Özcan Met; David Askmyr; Malin Lindstedt; Lennart Greiff; Laure-Anne Ligeon; Irina Agarkova; Inge Marie Svane; Cristiana F Pires; Fábio F Rosa; Carlos-Filipe Pereira

doi:10.1126/science.adn9083

In vivo dendritic cell reprogramming for cancer immunotherapy

Ervin Ascic
, Fritiof Åkerström
, Malavika Sreekumar Nair
, André Rosa
, Ilia Kurochkin
, Olga Zimmermannova
, Xavier Catena
, Nadezhda Rotankova
, Charlotte Veser
, Michal Rudnik
, Tommaso Ballocci
, Tiffany Schärer
, Xiaoli Huang
, Maria de Rosa Torres
, Emilie Renaud
, Marta Velasco Santiago
, Özcan Met
, David Askmyr
, Malin Lindstedt
, Lennart Greiff

Laure-Anne Ligeon, Irina Agarkova, Inge Marie Svane, Cristiana F Pires, Fábio F Rosa, Carlos-Filipe Pereira

129 Citations (Scopus)

Abstract

Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells; induced tumor regressions; and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.

Original language	English
Article number	eadn9083
Journal	Science (New York, N.Y.)
Volume	386
Issue number	6719
Pages (from-to)	eadn9083
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.adn9083
Publication status	Published - 18 Oct 2024

Keywords

Animals
Humans
Mice
Adenoviridae/genetics
Antigen Presentation
Basic-Leucine Zipper Transcription Factors/genetics
Cell Line, Tumor
Cellular Reprogramming/immunology
Dendritic Cells/cytology
Immunotherapy/methods
Interferon Regulatory Factors/metabolism
Melanoma/therapy
Melanoma, Experimental/therapy
Mice, Inbred C57BL
Repressor Proteins/genetics
T-Lymphocytes, Cytotoxic/immunology
Trans-Activators/genetics
Tumor Microenvironment/immunology
Cellular Reprogramming Techniques
Neoplasms/immunology

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10.1126/science.adn9083

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Ascic, E., Åkerström, F., Sreekumar Nair, M., Rosa, A., Kurochkin, I., Zimmermannova, O., Catena, X., Rotankova, N., Veser, C., Rudnik, M., Ballocci, T., Schärer, T., Huang, X., de Rosa Torres, M., Renaud, E., Velasco Santiago, M., Met, Ö., Askmyr, D., Lindstedt, M., ... Pereira, C.-F. (2024). In vivo dendritic cell reprogramming for cancer immunotherapy. Science (New York, N.Y.), 386(6719), eadn9083. Article eadn9083. https://doi.org/10.1126/science.adn9083

Ascic, E, Åkerström, F, Sreekumar Nair, M, Rosa, A, Kurochkin, I, Zimmermannova, O, Catena, X, Rotankova, N, Veser, C, Rudnik, M, Ballocci, T, Schärer, T, Huang, X, de Rosa Torres, M, Renaud, E, Velasco Santiago, M , Met, Ö, Askmyr, D, Lindstedt, M, Greiff, L, Ligeon, L-A, Agarkova, I, Svane, IM, Pires, CF, Rosa, FF & Pereira, C-F 2024, 'In vivo dendritic cell reprogramming for cancer immunotherapy', Science (New York, N.Y.), vol. 386, no. 6719, eadn9083, pp. eadn9083. https://doi.org/10.1126/science.adn9083

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abstract = "Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells; induced tumor regressions; and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.",

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doi = "10.1126/science.adn9083",

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T1 - In vivo dendritic cell reprogramming for cancer immunotherapy

AU - Ascic, Ervin

AU - Åkerström, Fritiof

AU - Sreekumar Nair, Malavika

AU - Rosa, André

AU - Kurochkin, Ilia

AU - Zimmermannova, Olga

AU - Catena, Xavier

AU - Rotankova, Nadezhda

AU - Veser, Charlotte

AU - Rudnik, Michal

AU - Ballocci, Tommaso

AU - Schärer, Tiffany

AU - Huang, Xiaoli

AU - de Rosa Torres, Maria

AU - Renaud, Emilie

AU - Velasco Santiago, Marta

AU - Met, Özcan

AU - Askmyr, David

AU - Lindstedt, Malin

AU - Greiff, Lennart

AU - Ligeon, Laure-Anne

AU - Agarkova, Irina

AU - Svane, Inge Marie

AU - Pires, Cristiana F

AU - Rosa, Fábio F

AU - Pereira, Carlos-Filipe

PY - 2024/10/18

Y1 - 2024/10/18

N2 - Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells; induced tumor regressions; and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.

AB - Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells; induced tumor regressions; and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.

KW - Animals

KW - Humans

KW - Mice

KW - Adenoviridae/genetics

KW - Antigen Presentation

KW - Basic-Leucine Zipper Transcription Factors/genetics

KW - Cell Line, Tumor

KW - Cellular Reprogramming/immunology

KW - Dendritic Cells/cytology

KW - Immunotherapy/methods

KW - Interferon Regulatory Factors/metabolism

KW - Melanoma/therapy

KW - Melanoma, Experimental/therapy

KW - Mice, Inbred C57BL

KW - Repressor Proteins/genetics

KW - T-Lymphocytes, Cytotoxic/immunology

KW - Trans-Activators/genetics

KW - Tumor Microenvironment/immunology

KW - Cellular Reprogramming Techniques

KW - Neoplasms/immunology

UR - https://www.scopus.com/pages/publications/85206133102

U2 - 10.1126/science.adn9083

DO - 10.1126/science.adn9083

M3 - Journal article

C2 - 39236156

SN - 0036-8075

VL - 386

SP - eadn9083

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6719

M1 - eadn9083

ER -

In vivo dendritic cell reprogramming for cancer immunotherapy

Abstract

Keywords

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