Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients

被引:230
作者
Parmiani, G.
Castelli, C.
Pilla, L.
Santinami, M.
Colombo, M. P.
Rivoltini, L.
机构
[1] Ist Nazl Tumori, Dept Innovat Therapies, Unit Ummunotherapy Human Tumors, I-20133 Milan, Italy
[2] Ist Nazl Tumori, Dept Surg, Unit Melanoma Sarcoma Surg, I-20133 Milan, Italy
[3] Ist Nazl Tumori, Unit Immunotherapy & Gene Therapy, I-20133 Milan, Italy
关键词
adjuvant; GM-CSF; immune stimulation; immune suppression; COLONY-STIMULATING FACTOR; COLORECTAL-CARCINOMA PATIENTS; PROSTATE-CANCER; TUMOR-CELLS; T-CELLS; ANTITUMOR IMMUNITY; PANCREATIC-CANCER; INTERFERON-GAMMA; MELANOMA-CELLS; PHASE-2; TRIAL;
D O I
10.1093/annonc/mdl158
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 mu g for 1-5 days) whereas an opposite effect was often reported at dosages of 100-500 mu g. 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.
引用
收藏
页码:226 / 232
页数:7
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