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Therapeutic efficacy of antitumor dendritic cell vaccinations correlates with persistent Th1 responses, high intratumor CD8+ T cell recruitment and low relative regulatory T cell infiltration

Cancer Immunology, Immunotherapy volume 57, pages 1745–1756 (2008)Cite this article

Abstract

Despite the increasing number of immunotherapeutic strategies for the treatment of cancer, most approaches have failed to correlate the induction of an anti-tumor immune response with therapeutic efficacy. We therefore took advantage of a successful vaccination strategy—combining dendritic cells and irradiated GM-CSF secreting tumor cells—to compare the immune response induced against 9L gliosarcoma tumors in cured rats versus those with progressively growing tumors. At the systemic level, the tumor specific cytotoxic responses were quite heterogeneous in uncured vaccinated rats, and were surprisingly often high in animals with rapidly-growing tumors. IFN-γ secretion by activated splenic T cells was more discriminative as the CD4+ T cell-mediated production was weak in uncured rats whereas high in cured ones. At the tumor level, regressing tumors were strongly infiltrated by CD8+ T cells, which demonstrated lytic capacities as high as their splenic counterparts. In contrast, progressing tumors were weakly infiltrated by T cells showing impaired cytotoxic activities. Proportionately to the T cell infiltrate, the expression of Foxp3 was increased in progressive tumors suggesting inhibition by regulatory T cells. In conclusion, the main difference between cured and uncured vaccinated animals does not depend directly upon the induction of systemic cytotoxic responses. Rather the persistence of higher CD4+ Th1 responses, a high intratumoral recruitment of functional CD8+ T cells, and a low proportion of regulatory T cells correlate with tumor rejection.

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Abbreviations

CTL:

Cytotoxic T lymphocytes

DC:

Dendritic cells

Treg:

Regulatory T cells

TIL:

Tumor-infiltrating lymphocytes

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Acknowledgments

We deeply thank the Dr J. Kline and Dr. G. Vassart for critical review of the manuscript.

Author information

Affiliations

  1. LCCE-IRIBHM, Faculty of Medicine, Université Libre de Bruxelles (ULB), route de Lennik 808, 1070, Bruxelles, Belgium

    Gregory Driessens, Lise Nuttin, Thierry Velu & Catherine Bruyns

  2. Department of Medical Oncology, Erasme Hospital, Université Libre de Bruxelles (ULB), route de Lennik 808, 1070, Brussels, Belgium

    Laurence Gordower, Patrick Stordeur & Thierry Velu

  3. Department of Nuclear Medicine, Erasme Hospital, Université Libre de Bruxelles (ULB), route de Lennik 808, 1070, Brussels, Belgium

    Didier Blocklet, Dominique Egrise & Thierry Velu

Authors
  1. Gregory Driessens
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  2. Laurence Gordower
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  3. Lise Nuttin
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  4. Patrick Stordeur
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  6. Dominique Egrise
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  7. Thierry Velu
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  8. Catherine Bruyns
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Corresponding author

Correspondence to Gregory Driessens.

Additional information

Grant support: G. Driessens was fellow of the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA), and Télévie. This work was supported by the Belgian State, Prime Minister’s office, Service for Science, Technology, and Culture, the Fonds National de la Recherche Scientifique, the Fonds de la Recherche Scientifique Médicale, the Actions de Recherche Concertées of the Communauté Française de Belgique and Télévie.

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Driessens, G., Gordower, L., Nuttin, L. et al. Therapeutic efficacy of antitumor dendritic cell vaccinations correlates with persistent Th1 responses, high intratumor CD8+ T cell recruitment and low relative regulatory T cell infiltration. Cancer Immunol Immunother 57, 1745–1756 (2008). https://doi.org/10.1007/s00262-008-0500-y

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  • DOI: https://doi.org/10.1007/s00262-008-0500-y

Keywords

  • T cells
  • Tumor immunity
  • Vaccination