Anti‐angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte‐endothelium interactions and infiltration in tumors

Dirkx, Anita E. M.; Egbrink, Mirjam G.A. oude; Castermans, Karolien; Schaft, Daisy W. J. van der; Thijssen, Victor L.; Dings, Ruud P.M.; Kwee, Lucy; Mayo, Kevin H.; Wagstaff, John; Steege, Jessica C. A. Bouma ter; Griffioen, Arjan W.

doi:10.1096/fj.05-4493com

Cited by 243 publications

(197 citation statements)

References 33 publications

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“…20--22 Leukocyte--vessel wall interactions are mediated by endothelial cell adhesion molecules, such as intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and CD34. 23 Dikxs et al 24 have demonstrated that angiogenesis inhibitors increase leukocyte--vessel wall interactions in tumor vessels, which lead to increased leukocyte infiltration into tumor tissue. Endogenous inhibitors of angiogenesis are proteins or protein fragments that are formed in the body and can inhibit the formation of blood vessels.…”

Section: Introductionmentioning

confidence: 99%

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

et al. 2012

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One of the greatest challenges in urological oncology is renal cell carcinoma (RCC), which is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and respond positively to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of ES-based antiangiogenic therapy to activate tumor-associated endothelial cells in metastatic RCC (mRCC). Balb/c-bearing Renca cells were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. The T-cell subsets and lymphocyte populations of tumors, mediastinal lymph nodes and the spleen were assessed by flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed by real-time PCR, flow cytometry and immunohistochemistry analysis. ES gene therapy led to an increase in the percentage of infiltrating CD4-interferon (IFN)-g cells (Po0.05), CD8-IFN-g cells (Po0.01) and CD49b-tumor necrosis factor-a cells (Po0.01). In addition, ES therapy caused an increase at the mRNA level of ICAM-1 (1.4-fold; Po0.01) and VCAM-1 (1.5-fold) (control vs treated group; Po0.001). Through flow cytometry, we found a significant increase in the CD34/ICAM-1 cells (8.1-fold; Po0.001) and CD34/VCAM-1 cells (1.6-fold; Po0.05). ES gene therapy induced a significant increase in both T CD4 and CD8 cells in the lymph nodes and the spleen, suggesting that ES therapy may facilitate cell survival or clonal expansion. CD49b cells were also present in increased quantities in all of these organs. In this study, we demonstrate an antitumor inflammatory effect of ES in an mRCC model, and this effect is mediated by an increase in ICAM-1 and VCAM-1 expression in tumor-associated endothelial cells.

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Section: Introductionmentioning

confidence: 99%

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

et al. 2012

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“…Immortalized human fetal tracheal cells (CFT-2, cell line carrying the homozygous mutation DF508, and NT-1, control cell line) were previously characterized [7,8]. Human umbilical vein endothelial cells (HUVEC) were isolated and cultured as previously described [9]. Only cells from passage 1 to 3 were used for experiments.…”

Section: Methodsmentioning

confidence: 99%

Intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells

Verhaeghe

Tabruyn

Oury

2007

Biochemical and Biophysical Research Communications

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Cystic fibrosis is a common genetic disorder characterized by a severe lung inflammation and fibrosis leading to the patient's death. Enhanced angiogenesis in cystic fibrosis (CF) tissue has been suggested, probably caused by the process of inflammation, as similarly described in asthma and chronic bronchitis. The present study demonstrates an intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells. Microarray experiments showed that CF airway epithelial cells expressed several angiogenic factors such as VEGF-A, VEGF-C, bFGF, and PLGF at higher levels than control cells. These data were confirmed by real-time quantitative PCR and, at the protein level, by ELISA. Conditioned media of these cystic fibrosis cells were able to induce proliferation, migration and sprouting of cultured primary endothelial cells. This report describes for the first time that cystic fibrosis epithelial cells have an intrinsic angiogenic activity. Since excess of angiogenesis is correlated with more severe pulmonary disease, our results could lead to the development of new therapeutic applications.

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“…A few experimental studies have shown that endogenous T cell infiltration is increased following anti-angiogenic agents [153][154][155], and one study has shown that the efficacy of DC101 treatment is dependent on both CD4 + and CD8 + T cells in a transplantable mammary tumor model [153]. As such, the need for more investigations into the role of immunosuppressive and adaptive immune cells is warranted to help guide the future clinical possibility of combining vascular-targeting agents with immunotherapy.…”

Section: Much Less Is Known About the Role Of Tregs And T Cells Durinmentioning

confidence: 99%

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

Coffelt

Visser

2015

Trends in Immunology

125

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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...

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Anti‐angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte‐endothelium interactions and infiltration in tumors

Cited by 243 publications

References 33 publications

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

Intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

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