Role of GM-CSF signaling in cell-based tumor immunization

Zarei, Shohreh; Schwenter, Frank; Luy, P.; Aurrand-Lions, Michel; Morel, Philippe; Köpf, Manfred; Dranoff, Glenn; Mach, Nicolas

doi:10.1182/blood-2008-06-161075

Cited by 35 publications

(33 citation statements)

References 48 publications

(57 reference statements)

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“…Many studies have outlined the beneficial effects of probiotics on various aliments such as food allergies (Kalliomäki and Isolauri, 2003), inflammatory bowel disease, and ulcerative colitis (Stephani et al, 2011). Probiotics exert their modulatory actions by different mechanisms, including: anti-genotoxicity; inhibition of colonic enzyme activity, which reduces the harmful effects of carcinogens activated by enzymatic action in the colon (Liong, 2008); control of the growth of potentially harmful bacteria (Zarei et al, 2009); interaction with colonocytes; and enhancement of homeostasis and the integrity of the epithelial barrier. Recently, research by Hijová et al (2012) on colon cancer rats has indicated that prebiotics have a protective effect and may be useful for colon cancer prevention and treatment.…”

Section: Introductionmentioning

confidence: 99%

Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model

et al. 2015

Genet. Mol. Res.

215

120

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ABSTRACT. The intestinal microflora affects inflammation and immunity, not only locally at the mucosal level but also systemically, raising the question of whether the microflora affects inflammatory processes that contribute to cancer and its therapy. Prebiotics have also been found to play an antitumor role that is not limited to the gut. We investigated the antitumor roles of the intestinal microbiota using the Lewis lung cancer mouse model. In mice treated with cisplatin combined with ABX (an antibiotic cocktail of vancomycin, ampicillin, and neomycin), which can destroy the host commensal microflora, the tumor size was larger than in mice on a single treatment of cisplatin. Moreover, the survival rate of mice treated with cisplatin combined with ABX was significantly reduced. In contrast, mice treated with cisplatin combined with Lactobacillus bacteria had smaller tumors and an improved survival rate. Further study on gene expression indicated that ABX can partially impair the function of cisplatin by upregulating the expression of VEGFA and downregulating the expression of BAX 5643Commensal microbiota contributes to lung cancer immunity ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research X (X): XXX-XXX (2015) and CDKN1B. The expression of IFN-γ, GZMB, and PRF1 in the CD8 + T cells of these mice was reduced by ABX, indicating an immunoenhancement role of commensal microbiota. Conversely, Lactobacillus co-treatment mice showed an enhanced antitumor response with upregulated IFN-γ, GZMB, and PRF1 expression. We conclude that the commensal microbiota contributes to the anti-lung cancer response and probiotics co-treatment can enhance the antigrowth and proapoptotic effects of cisplatin.

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Section: Introductionmentioning

confidence: 99%

Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model

et al. 2015

Genet. Mol. Res.

215

120

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“…6,7 Among all adjuvants, toll-like receptor (TLR) agonists and cytokines including GM-CSF have been tested in both preclinical and clinical settings for cancer treatment. 8,9 However, some adjuvants may have tumor-promoting effects, for example, TLR4 ligation enhances immunosuppressive cytokine production by human lung cancer cells. 10 High dose of GM-CSF has been shown to chemoattract MDSCs thus dampening the efficacy of cancer vaccines.…”

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confidence: 99%

Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived β-glucans

Cai

Gunn

et al. 2011

Blood

212

157

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β-glucans have been reported to function as a potent adjuvant to stimulate innate and adaptive immune responses. However, β-glucans from different sources are differential in their structure, conformation, and thus biologic activity. Different preparations of β-glucans, soluble versus particulate, further complicate their mechanism of action. Here we show that yeast-derived particulate β-glucan activated dendritic cells (DCs) and macrophages via a C-type lectin receptor dectin-1 pathway. Activated DCs by particulate β-glucan promoted Th1 and cytotoxic T-lymphocyte priming and differentiation in vitro. Treatment of orally administered yeast-derived particulate β-glucan elicited potent antitumor immune responses and drastically down-regulated immunosuppressive cells, leading to the delayed tumor progression. Deficiency of the dectin-1 receptor completely abrogated particulate β-glucan-mediated antitumor effects. In contrast, yeast-derived soluble β-glucan bound to DCs and macrophages independent of the dectin-1 receptor and did not activate DCs. Soluble β-glucan alone had no therapeutic effect but significantly augmented antitumor monoclonal antibody-mediated therapeutic efficacy via a complement activation pathway but independent of dectin-1 receptor. These findings reveal the importance of different preparations of β-glucans in the adjuvant therapy and allow for the rational design of immunotherapeutic protocols usable in clinical trials.

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“…Despite a body of literature that supports use of GM-CSF as a vaccine adjuvant [4, 39, 40], two prospective randomized phase II trials have shown negative effects of GM-CSF in combination with other vaccine adjuvants [21, 41]. The overall CTL response rates (43 and 47% in Arms A and B) are based on ELIspot assays performed after in vitro stimulation; which has been required for other studies when GM-CSF was used in the adjuvant [4, 20, 21]; we expect that the magnitude of these responses would be greater using IFA without GM-CSF.…”

Section: Discussionmentioning

confidence: 99%

A Randomized Phase II Trial of Multiepitope Vaccination with Melanoma Peptides for Cytotoxic T Cells and Helper T Cells for Patients with Metastatic Melanoma (E1602)

Slingluff

Lee

Zhao

et al. 2013

Clinical Cancer Research

105

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Purpose This multicenter randomized trial was designed to evaluate whether melanoma helper peptides augment cytotoxic T-lymphocyte (CTL) responses to a melanoma vaccine and improve clinical outcome in patients with advanced melanoma. Patients and Methods One hundred seventy-five patients with measurable stage IV melanoma were enrolled into 4 treatment groups, vaccinated with 12 MHC Class I-restricted melanoma peptides (12MP) to stimulate CTL (group A), plus a tetanus peptide (group B) or a mixture of 6 melanoma helper peptides (6MHP, group C) to stimulate helper T lymphocytes (HTL), or with 6MHP alone (group D), in incomplete Freund’s adjuvant (IFA) plus GM-CSF. CTL responses were assessed using an in vitro stimulated IFN-gamma ELIspot assay, and HTL responses using proliferation assay. Results In groups A–D, respectively, CTL response rates to 12MP were 43%, 47%, 28%, and 5%, and HTL response rates to 6MHP were in 3%, 0%, 40% and 41%. Best clinical response was partial response (PR) in 7/148 evaluable patients (4.7%) without significant difference among study arms. Median overall survival (OS) was 11.8 months. Immune response to 6MHP was significantly associated with both clinical response (p=0.036) and OS (p=0.004). Conclusion Each vaccine regimen was immunogenic, but melanoma helper peptides did not augment CTL responses to 12MP. The association of survival and immune response to 6MHP supports further investigation of helper peptide vaccines. For patients with advanced melanoma, multipeptide vaccines should be studied in combination with other potentially synergistic active therapies.

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Role of GM-CSF signaling in cell-based tumor immunization

Abstract: Granulocyte-macrophage colonystimulating factor (GM-CSF) is a potent adjuvant in cancer vaccination; however, the specific role of endogenous GM-CSF remains unknown. We performed cellbased vaccination in 2 tumor models.

Cited by 35 publications

References 48 publications

Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model

Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model

Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived β-glucans

A Randomized Phase II Trial of Multiepitope Vaccination with Melanoma Peptides for Cytotoxic T Cells and Helper T Cells for Patients with Metastatic Melanoma (E1602)

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