Annals of Oncology Advance Access originally published online on November 20, 2006
Annals of Oncology 2007 18(2):226-232; doi:10.1093/annonc/mdl158
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© 2006 European Society for Medical Oncology
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Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients
1 Unit of Immunotherapy of Human Tumors, Department of Innovative Therapies
2 Unit of Melanoma/Sarcoma Surgery, Department of Surgery
3 Unit of Immunotherapy and Gene Therapy, Istituto Nazionale Tumori, Milan, Italy
* Correspondence to: Dr G. Parmiani, Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milan, Italy. Tel: +39–02–23902328; E-mail: giorgio.parmiani{at}istitutotumori.mi.it
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been and is still widely used as an adjuvant in clinical trials of vaccination with autologous tumor cells, peptides and/or dendritic cells in a variety of human neoplasms. This cytokine was administered either as product of gene-transduced tumor cells or as recombinant protein together with the vaccine given subcutaneously or intradermally. Results of these trials were heterogeneous in terms of induction of vaccine-specific immune response and of clinical response. Though in some of these studies GM-CSF appeared to help in generating an immune response, in others no effect or even a suppressive effect was reported. Here, we review the literature dealing with the immune adjuvant activity of GM-CSF both in animal models and clinical trials. As a consequence of such analysis, we conclude that GM-CSF may increase the vaccine-induced immune response when administered repeatedly at relatively low doses (range 40–80 µg for 1–5 days) whereas an opposite effect was often reported at dosages of 100–500 µg. The potential mechanisms of the GM-CSF-mediated immune suppression are discussed at the light of studies describing the activation and expansion of myeloid suppressor cells by endogenous tumor-derived or exogenous GM-CSF.
Key words: adjuvant, GM-CSF, immune stimulation, immune suppression
Received for publication May 18, 2006. Accepted for publication May 29, 2006.
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