The colony-stimulating factors and cancer

Metcalf, Donald

doi:10.1038/nrc2843

Cited by 136 publications

(92 citation statements)

References 150 publications

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“…In this context, in a pre-clinical study of GM-CSF therapy for atherosclerosis in rabbits, there were features suggesting accelerated advanced plaque progression despite a decrease in overall intimal area 10 . Fourth, GM-CSF is administered to cancer patients following chemotherapy to mobilize stem cells 11 , while anti-GM-CSF therapy is under trial for treatment of rheumatoid arthritis and multiple sclerosis 12 . Because these treatments are offered to patients who may have sub-clinical coronary artery disease, it is important to understand the role of GM-CSF in advanced plaque progression.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Non-Growth Factor Role for GM-CSF in Advanced Atherosclerosis

Subramanian

Thorp

Tabas

2015

Circulation Research

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Rationale Granulocyte macrophage colony stimulating factor (GM-CSF, Csf2) is a growth factor for myeloid-lineage cells that has been implicated in the pathogenesis of atherosclerosis and other chronic inflammatory diseases. However, the role of GM-CSF in advanced atherosclerotic plaque progression—the process that gives rise to clinically dangerous plaques—is unknown. Objective To understand the role of GM-CSF in advanced atherosclerotic plaque progression. Methods and Results Ldlr−/− mice and Csf2−/−Ldlr−/− mice were fed a Western-type diet for 12 wks, and then parameters of advanced plaque progression in the aortic root were quantified. Lesions from the GM-CSF-deficient mice showed a substantial decrease in two key hallmarks of advanced atherosclerosis, lesional macrophage apoptosis and plaque necrosis, which indicates that GM-CSF promotes plaque progression. Based on a combination of in vitro and in vivo studies, we show that the mechanism involves GM-CSF-mediated production of IL-23, which increases apoptosis susceptibility in macrophages by promoting proteasomal degradation of the cell-survival protein Bcl-2 and by increasing oxidative stress. Conclusion In LDL-driven atherosclerosis in mice, GM-CSF promotes advanced plaque progression by increasing macrophage apoptosis susceptibility. This action of GM-CSF is mediated by its IL-23-inducing activity rather than its role as a growth factor.

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Section: Introductionmentioning

confidence: 99%

Identification of a Non-Growth Factor Role for GM-CSF in Advanced Atherosclerosis

Subramanian

Thorp

Tabas

2015

Circulation Research

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“…[9][10][11][12] Owing to their capacity to regulate various cellular responses including proliferation, differentiation, activation and regulated cell death, cytokines orchestrate complex organismal functions as different as hematopoiesis, angiogenesis, wound healing and inflammation. [13][14][15][16][17][18][19] Moreover, some cytokines play a critical role in the initiation, propagation and extinction of innate and adaptive immune responses, irrespective of whether such responses are initiated by microbial challenges or endogenous states of danger. [20][21][22] As a standalone example, Type I interferon (IFN) is not only a key determinant of antiviral immunity, 21,22 but also an important mediator of immune responses elicited by cancer cells undergoing so-called "immunogenic cell death" (ICD).…”

Section: Introductionmentioning

confidence: 99%

Trial Watch—Immunostimulation with cytokines in cancer therapy

Vacchelli¹,

Aranda

Bloy³

et al. 2015

OncoImmunology

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During the past decade, great efforts have been dedicated to the development of clinically relevant interventions that would trigger potent (and hence potentially curative) anticancer immune responses. Indeed, developing neoplasms normally establish local and systemic immunosuppressive networks that inhibit tumor-targeting immune effector cells, be them natural or elicited by (immuno)therapy. One possible approach to boost anticancer immunity consists in the (generally systemic) administration of recombinant immunostimulatory cytokines. In a limited number of oncological indications, immunostimulatory cytokines mediate clinical activity as standalone immunotherapeutic interventions. Most often, however, immunostimulatory cytokines are employed as immunological adjuvants, i.e., to unleash the immunogenic potential of other immunotherapeutic agents, like tumor-targeting vaccines and checkpoint blockers. Here, we discuss recent preclinical and clinical advances in the use of some cytokines as immunostimulatory agents in oncological indications.

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“…This holds true for FDA approved GM-CSF (2–4) and IL-2 (5). Nevertheless, cytokine-based cancer immunotherapy remains an active area of clinical research.…”

Section: Introductionmentioning

confidence: 86%

Engineered Fusokine GIFT4 Licenses the Ability of B Cells to Trigger a Tumoricidal T-cell Response

et al. 2014

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Engineered chimeric cytokines can generate gain-of-function activity in immune cells. Here we report potent antitumor activity for a novel fusion cytokine generated by N-terminal coupling of GM-CSF to IL-4, generating a fusokine termed GIFT4. B cells treated with GIFT4 clustered GM-CSF and IL-4 receptors on the cell surface and displayed a pan-STAT hyperphosphorylation associated with acquisition of a distinct phenotype and function described to date. In C57BL/6J mice, administration of GIFT4 expanded endogenous B cells and suppressed the growth of B16F0 melanoma cells. Further, B16F0 melanoma cells engineered to secrete GIFT4 were rejected immunologically in a B cell-dependent manner. This effect was abolished when GIFT4-expressing B16F0 cells were implanted in B cell-deficient mice, confirming a B cell-dependent antitumor effect. Human GIFT4-licensed B cells primed cytotoxic T cells and specifically killed melanoma cells in vitro and in vivo. Taken together, our results demonstrated that GIFT4 could mediate expansion of B cells with potent antigen-specific effector function. GIFT4 may offer a novel immunotherapeutic tool and define a previously unrecognized potential for B cells in melanoma immunotherapy.

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The colony-stimulating factors and cancer

Cited by 136 publications

References 150 publications

Identification of a Non-Growth Factor Role for GM-CSF in Advanced Atherosclerosis

Identification of a Non-Growth Factor Role for GM-CSF in Advanced Atherosclerosis

Trial Watch—Immunostimulation with cytokines in cancer therapy

Engineered Fusokine GIFT4 Licenses the Ability of B Cells to Trigger a Tumoricidal T-cell Response

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