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T cells are crucial for the anti-metastatic effect of anti-epidermal growth factor receptor antibodies

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Abstract

Experimental evidences supporting the epidermal growth factor receptor (EGFR) as an important molecule for tumor metastasis had been accumulated. Currently, anti-EGFR monoclonal antibodies (mAbs) constitute a promising approach for the treatment of patients with metastatic tumors. However, the mechanisms associated with the potent anti-metastatic effect of these mAbs have not been completely elucidated due to the lack of appropriate syngeneic preclinical models. In this paper, we have investigated the effects of 7A7, an antibody specific to murine EGFR, on the metastatic properties of D122 murine lung carcinoma. 7A7 mAb significantly impaired metastatic spread of D122 cells in C57BL/6 mice by direct anti-proliferative and pro-apoptotic effects on tumor metastasis. 7A7 mAb capacity to inhibit EGFR activation on D122 cells could contribute to its anti-metastatic effect. In addition, 7A7 mAb was able to induce in vitro antibody-dependent cell-mediated cytotoxicity on D122 cells. Interestingly, 7A7 mAb treatment increased the number of natural killer cells, T lymphocytes and dendritic cells infiltrating the metastatic sites. More strikingly, depletion of CD8+ and CD4+ T cells in vivo completely abrogated the 7A7 mAb anti-metastatic activity whereas function of natural killer cells was irrelevant. This study supports an in vivo role for T cell response in the mechanism of action of anti-EGFR mAbs, suggesting the induction of an adjuvant effect.

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Abbreviations

EGFR:

Epidermal growth factor receptor

mAb:

Monoclonal antibody

EGF:

Epidermal growth factor

PARP:

Poly (ADP-ribose) polymerase

STAT 3:

Signal transducer and activator of transcription 3

FBS:

Fetal bovine serum

PI:

Propidium iodide

ADCC:

Antibody-dependent cell-mediated cytotoxicity

MAPK:

Mitogen-activated protein kinase

PI3–K:

Phosphotidylinositol-3 kinase

NK:

Natural killer

DC:

Dendritic cell

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Acknowledgments

We thank Armando López (Center of Molecular Immunology) for their excellent technical assistance with animal experiments.

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Authors and Affiliations

  1. Vaccine Department, Center of Molecular Immunology, 216 St and 15th Ave., Atabey, Siboney, Playa, P.O. Box 16040, Havana, 11600, Cuba

    Greta Garrido, Belinda Sánchez, Irene Beausoleil, Rolando Pérez & Luis E. Fernández

  2. Molecular Oncology Laboratory, Quilmes National University, R. Saenz Peña 352 (ex180), Bernal, B1876BXD, Buenos Aires, Argentina

    Pablo Lorenzano & Daniel F. Alonso

Authors
  1. Greta Garrido
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  2. Pablo Lorenzano
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  3. Belinda Sánchez
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  4. Irene Beausoleil
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  5. Daniel F. Alonso
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  6. Rolando Pérez
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  7. Luis E. Fernández
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Corresponding author

Correspondence to Greta Garrido.

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This work was supported by the Cuban Government.

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Garrido, G., Lorenzano, P., Sánchez, B. et al. T cells are crucial for the anti-metastatic effect of anti-epidermal growth factor receptor antibodies. Cancer Immunol Immunother 56, 1701–1710 (2007). https://doi.org/10.1007/s00262-007-0313-4

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  • DOI: https://doi.org/10.1007/s00262-007-0313-4

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