Advanced search
1 file | 8.06 MB Add to list

A bispecific Clec9A-PD-L1 targeted type I interferon profoundly reshapes the tumor microenvironment towards an antitumor state

Sandra Van Lint (UGent) , Alexander Van Parys (UGent) , Bram Van Den Eeckhout (UGent) , Niels Vandamme (UGent) , Stephane Plaisance, Annick Verhee (UGent) , Dominiek Catteeuw (UGent) , Elke Rogge (UGent) , Jennifer De Geest (UGent) , Nele Vanderroost (UGent) , et al.
Author
Organization
Project
Abstract
Despite major improvements in immunotherapeutic strategies, the immunosuppressive tumor microenvironment remains a major obstacle for the induction of efficient antitumor responses. In this study, we show that local delivery of a bispecific Clec9A-PD-L1 targeted type I interferon (AcTaferon, AFN) overcomes this hurdle by reshaping the tumor immune landscape. Treatment with the bispecific AFN resulted in the presence of pro-immunogenic tumor-associated macrophages and neutrophils, increased motility and maturation profile of cDC1 and presence of inflammatory cDC2. Moreover, we report empowered diversity in the CD8+ T cell repertoire and induction of a shift from naive, dysfunctional CD8+ T cells towards effector, plastic cytotoxic T lymphocytes together with increased presence of NK and NKT cells as well as decreased regulatory T cell levels. These dynamic changes were associated with potent antitumor activity. Tumor clearance and immunological memory, therapeutic immunity on large established tumors and blunted tumor growth at distant sites were obtained upon co-administration of a non-curative dose of chemotherapy. Overall, this study illuminates further application of type I interferon as a safe and efficient way to reshape the suppressive tumor microenvironment and induce potent antitumor immunity; features which are of major importance in overcoming the development of metastases and tumor cell resistance to immune attack. The strategy described here has potential for application across to a broad range of cancer types.
Keywords
Cancer Research, Oncology, Molecular Medicine, Immune checkpoint, Cancer immunotherapy, Tumor microenvironment, AcTakine, Type I Interferon

Downloads

  • s12943-023-01908-6.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 8.06 MB

Citation

Please use this url to cite or link to this publication:

MLA
Van Lint, Sandra, et al. “A Bispecific Clec9A-PD-L1 Targeted Type I Interferon Profoundly Reshapes the Tumor Microenvironment towards an Antitumor State.” MOLECULAR CANCER, vol. 22, no. 1, Springer Science and Business Media LLC, 2023, doi:10.1186/s12943-023-01908-6.
APA
Van Lint, S., Van Parys, A., Van Den Eeckhout, B., Vandamme, N., Plaisance, S., Verhee, A., … Tavernier, J. (2023). A bispecific Clec9A-PD-L1 targeted type I interferon profoundly reshapes the tumor microenvironment towards an antitumor state. MOLECULAR CANCER, 22(1). https://doi.org/10.1186/s12943-023-01908-6
Chicago author-date
Van Lint, Sandra, Alexander Van Parys, Bram Van Den Eeckhout, Niels Vandamme, Stephane Plaisance, Annick Verhee, Dominiek Catteeuw, et al. 2023. “A Bispecific Clec9A-PD-L1 Targeted Type I Interferon Profoundly Reshapes the Tumor Microenvironment towards an Antitumor State.” MOLECULAR CANCER 22 (1). https://doi.org/10.1186/s12943-023-01908-6.
Chicago author-date (all authors)
Van Lint, Sandra, Alexander Van Parys, Bram Van Den Eeckhout, Niels Vandamme, Stephane Plaisance, Annick Verhee, Dominiek Catteeuw, Elke Rogge, Jennifer De Geest, Nele Vanderroost, Jana Roels, Yvan Saeys, Gilles Uzé, Niko Kley, Anje Cauwels, and Jan Tavernier. 2023. “A Bispecific Clec9A-PD-L1 Targeted Type I Interferon Profoundly Reshapes the Tumor Microenvironment towards an Antitumor State.” MOLECULAR CANCER 22 (1). doi:10.1186/s12943-023-01908-6.
Vancouver
1.
Van Lint S, Van Parys A, Van Den Eeckhout B, Vandamme N, Plaisance S, Verhee A, et al. A bispecific Clec9A-PD-L1 targeted type I interferon profoundly reshapes the tumor microenvironment towards an antitumor state. MOLECULAR CANCER. 2023;22(1).
IEEE
[1]
S. Van Lint et al., “A bispecific Clec9A-PD-L1 targeted type I interferon profoundly reshapes the tumor microenvironment towards an antitumor state,” MOLECULAR CANCER, vol. 22, no. 1, 2023.
@article{01HGFSFPXFC0Q52DJFZTE51ZBR,
  abstract     = {{Despite major improvements in immunotherapeutic strategies, the immunosuppressive tumor microenvironment remains a major obstacle for the induction of efficient antitumor responses. In this study, we show that local delivery of a bispecific Clec9A-PD-L1 targeted type I interferon (AcTaferon, AFN) overcomes this hurdle by reshaping the tumor immune landscape.

Treatment with the bispecific AFN resulted in the presence of pro-immunogenic tumor-associated macrophages and neutrophils, increased motility and maturation profile of cDC1 and presence of inflammatory cDC2. Moreover, we report empowered diversity in the CD8+ T cell repertoire and induction of a shift from naive, dysfunctional CD8+ T cells towards effector, plastic cytotoxic T lymphocytes together with increased presence of NK and NKT cells as well as decreased regulatory T cell levels. These dynamic changes were associated with potent antitumor activity. Tumor clearance and immunological memory, therapeutic immunity on large established tumors and blunted tumor growth at distant sites were obtained upon co-administration of a non-curative dose of chemotherapy.

Overall, this study illuminates further application of type I interferon as a safe and efficient way to reshape the suppressive tumor microenvironment and induce potent antitumor immunity; features which are of major importance in overcoming the development of metastases and tumor cell resistance to immune attack. The strategy described here has potential for application across to a broad range of cancer types.}},
  articleno    = {{191}},
  author       = {{Van Lint, Sandra and Van Parys, Alexander and Van Den Eeckhout, Bram and Vandamme, Niels and Plaisance, Stephane and Verhee, Annick and Catteeuw, Dominiek and Rogge, Elke and De Geest, Jennifer and Vanderroost, Nele and Roels, Jana and Saeys, Yvan and Uzé, Gilles and Kley, Niko and Cauwels, Anje and Tavernier, Jan}},
  issn         = {{1476-4598}},
  journal      = {{MOLECULAR CANCER}},
  keywords     = {{Cancer Research,Oncology,Molecular Medicine,Immune checkpoint,Cancer immunotherapy,Tumor microenvironment,AcTakine,Type I Interferon}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{21}},
  publisher    = {{Springer Science and Business Media LLC}},
  title        = {{A bispecific Clec9A-PD-L1 targeted type I interferon profoundly reshapes the tumor microenvironment towards an antitumor state}},
  url          = {{http://doi.org/10.1186/s12943-023-01908-6}},
  volume       = {{22}},
  year         = {{2023}},
}

Altmetric
View in Altmetric
Web of Science
Times cited: