Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients.
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 microg for 1-5 days) whereas an opposite effect was often reported at dosages of 100-500 microg. 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.
Parmiani
G
G
Unit of Immunotherapy of Human Tumors, Department of Innovative Therapies, Istituto Nazionale Tumori, Milan, Italy. giorgio.parmiani@istitutotumori.mi.it
Castelli
C
C
Pilla
L
L
Santinami
M
M
Colombo
M P
MP
Rivoltini
L
L
D000276:Adjuvants, Immunologic; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor