HIF1α Induces the Recruitment of Bone Marrow-Derived Vascular Modulatory Cells to Regulate Tumor Angiogenesis and Invasion

Du, Rose; Lu, Kan V.; Petritsch, Claudia; Liu, Patty; Ganss, Ruth; Passegué, Emmanuelle; Song, Hanqiu; VandenBerg, Scott R.; Johnson, Randall S.; Werb, Zena; Bergers, Gabriele

doi:10.1016/j.ccr.2008.01.034

Cited by 1,037 publications

(956 citation statements)

References 56 publications

Supporting

Mentioning

909

Contrasting

Unclassified

Order By: Relevance

“…The GL261-Quad cell line is engineered to express the model antigens human gp100 [25][26][27][28][29][30][31][32][33] , chicken OVA 257-264 , chicken OVA [323][324][325][326][327][328][329][330][331][332][333][334][335][336][337][338][339] , and mouse alloantigen I-Ea [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] . Female 6-8-week-old C57BL/6 mice (The Jackson Laboratory, Bar Harbor, ME, USA) were inoculated by stereotactic injection of 6.0×10 4 -1.0×10 5 GL261 or GL261-Quad cells into the right striatum.…”

Section: Gl261 Tumor Implantationmentioning

confidence: 99%

Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model

et al. 2016

View full text Add to dashboard Cite

The addition of antiangiogenic therapy to the standard-of-care treatment regimen for recurring glioblastoma has provided some clinical benefits while also delineating numerous caveats, prompting evaluation of the elicited alterations to the tumor microenvironment. Of critical importance, given the steadily increasing incorporation of immunotherapeutic approaches clinically, is an enhanced understanding of the interplay between angiogenic and immune response pathways within tumors. In the present study, the GL261 glioma mouse model was used to determine the effects of antiangiogenic treatment in an immune-competent host. Following weekly systemic administration of aflibercept, an inhibitor of vascular endothelial growth factor, tumor volume was assessed by magnetic resonance imaging and changes to the tumor microenvironment were determined. Treatment with aflibercept resulted in reduced tumor burden and increased survival compared with controls. Additionally, decreased vascular permeability and preservation of the integrity of tight junction proteins were observed. Treated tumors also displayed hallmarks of anti-angiogenic evasion, including marked upregulation of vascular endothelial growth factor expression and increased tumor invasiveness. Aflibercept was then administered in combination with a picornavirusbased antitumor vaccine and tumor progression was evaluated. This combination therapy significantly delayed tumor progression and extended survival beyond that observed for either therapy alone. As such, this work demonstrates the efficacy of combined antiangiogenic and immunotherapy approaches for treating established gliomas and provides a foundation for further evaluation of the effects of antiangiogenic therapy in the context of endogenous or vaccine-induced inflammatory responses.

show abstract

Section: Gl261 Tumor Implantationmentioning

confidence: 99%

Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model

et al. 2016

View full text Add to dashboard Cite

show abstract

“…More recent studies have shown that TAMs are recruited to experimental tumors following different forms of anti-angiogenic therapies [138][139][140], often because of the hypoxia-induced increase in chemotactic factors [94,138]. Various studies have reported that TAMs counteract the efficacy of anti-angiogenic agents.…”

Section: Immune Cell Function Following Vascular-targeting Agentsmentioning

confidence: 99%

“…In mice, radiotherapy-induced TAM infiltration is mainly attributed to radiation-induced hypoxia and the subsequent surge in hypoxia-regulated chemokines, such as CXCL12 [90,93]. Monocytes and macrophages expressing TIE2 -the receptor for Angiopoietins 1 and 2 -are highly receptive to increased hypoxia and CXCL12 levels [90,93,94], and TIE2-expressing monocytes/macrophages 10 have a profound ability to counteract hypoxia through the induction of angiogenesis [95]. As one may predict, neutralizing CXCL12 or blocking its receptor, CXCR4, to prevent TAM accumulation further delays tumor progression when combined with radiotherapy in orthotopic syngeneic and xenograft models of glioblastoma [90], as well as subcutaneous xenografts of lung carcinoma and syngeneic mammary tumors [93].…”

mentioning

confidence: 99%

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

Coffelt

Visser

2015

Trends in Immunology

125

View full text Add to dashboard Cite

SummaryConventional anti-cancer therapies, such as chemotherapy, radiotherapy and targeted therapy, are designed to kill cancer cells. Yet, the efficacy of anti-cancer therapies is not only determined by their direct effects on cancer cells, but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit a number of changes in immune-related parameters including the composition, phenotype and function of immune cells. In this review, we discuss the impact of innate and adaptive immune cells on the success of anti-cancer therapy, we examine the opportunities to exploit host immune responses to boost tumor clearing and we highlight the challenges facing the treatment of advanced metastatic disease. Then and now: The link between the immune system and anti-cancer therapiesThe relationship between anti-cancer therapies and the immune system is as old as the invention of anti-cancer therapies themselves. After the use of mustard gas in the trenches of World War I, a seminal observation was made that some exposed soldiers displayed severe loss of bone marrow and lymph node cells [1]. This observation then spurred the idea that the anti-proliferative capacity of mustard gas may also slow the growth of cancer cells.Experiments carried out in mice transplanted with lymphoid tumors were convincing enough to treat a lymphoma patient [2], and these events initiated the standardized treatment of cancer patients with chemotherapy [3,4].Fast forward 100 years later. The influence of immune cells on tumor progression and metastasis is well established [5], and an appreciation for the immune system's impact during conventional anti-cancer therapy treatment is growing. Recent seminal advances indicate that immune cells can shape the outcome of various anti-cancer therapies. As such, 2 immune cells and their molecular mediators have evolved into bona vide targets of therapeutic manipulation in cancer patients. The recent breakthrough of immunotherapeutics that inhibit negative immune regulatory pathways, such as anti-CTLA4 and anti-PD1, has initiated a new era in the treatment of cancer [6]. In parallel, immunomodulatory strategies aimed at dampening pro-tumor functions of immune cells are currently being tested in cancer patients [7]. Immune cells also function as reliable biomarkers, since their abundance or activation status often predicts how well patients respond to a particular treatment regimen.Here, we review these novel experimental and clinical insights, highlighting potential implications for the development of synergistic therapies designed to combat primary tumors and, more importantly, metastatic disease. The pros and cons of experimental mouse modelsResearch questions aimed at understanding the role of immune cells during anti-cancer therapy require models that mirror the complex interactions between the immune system and diverse forms of human cancers. Transplantable cancer cell line models and carcinogeninduced cancer models are the most frequently used for these purposes. However...

show abstract

“…[4][5][6][7] Considered chief among these is VEGF, which may be upregulated via multiple angiogenesispromoting pathways. In hypoxic conditions, commonly found as tumors outgrow their intrinsic blood supply, hypoxiainducible factor 1a accumulates and ultimately increases VEGF stabilization.…”

Section: Angiogenesis and The Role Of Antiangiogenesis In Patients Wimentioning

confidence: 99%

Bevacizumab and glioblastoma: Scientific review, newly reported updates, and ongoing controversies

Field

Jordan

Wen

et al. 2014

Cancer

View full text Add to dashboard Cite

Anti-angiogenic therapy for glioblastoma has been in the spotlight for several years, as researchers and clinicians strive to find agents with meaningful efficacy against glioblastoma. Bevacizumab in particular, in the second half of the last decade, became the most significant breakthrough in anti-glioblastoma therapy since temozolomide. Optimism for bevacizumab has been somewhat challenged given recent clinical trials that have raised questions regarding its clinical effectiveness, the optimal timing of its use and the validity of endpoints, among other issues. In addition, uncertainty has recently arisen regarding the effects of bevacizumab on quality of life and neurocognitive function, two key clinical endpoints of unquestionable significance among glioblastoma patients. In this review, we highlight these controversies and other recent work related to bevacizumab for glioblastoma. Cancer 2015;121:997

show abstract

HIF1α Induces the Recruitment of Bone Marrow-Derived Vascular Modulatory Cells to Regulate Tumor Angiogenesis and Invasion

Cited by 1,037 publications

References 56 publications

Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model

Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

Bevacizumab and glioblastoma: Scientific review, newly reported updates, and ongoing controversies

Contact Info

Product

Resources

About