A novel liposomal Clodronate depletes tumor-associated macrophages in primary and metastatic melanoma: Anti-angiogenic and anti-tumor effects

Piaggio, Francesca; Kondylis, Vangelis; Pastorino, Fabio; Paolo, Daniela Di; Perri, Patrizia; Cossu, Irene; Schorn, Fabian; Marinaccio, Christian; Murgia, Daniele; Daga, Antonio; Raggi, Federica; Loi, Monica; Emionite, Laura; Ognio, Emanuela; Pasparakis, Manolis; Ribatti, Doménico; Ponzoni, Mirco; Brignole, Chiara

doi:10.1016/j.jconrel.2015.12.037

Cited by 96 publications

(66 citation statements)

References 43 publications

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“…Clodronate-liposome treatment in murine F9 teratocarcinoma and human A673 Ewing’s sarcoma tumor models efficiently depleted TAMs and significantly inhibited tumor growth (Zeisberger et al 2006 ). Recently, an antimacrophage activity of liposomal clodronate has been confirmed in a hepatocarcinoma mouse model (Piaggio et al 2016 ). Moreover, depletion of TAMs with clodronate-loaded liposomes increased the antiangiogenic and antitumor effects of anti-VEGF antibodies in subcutaneous tumor models (Priceman et al 2010 ).…”

Section: Decreasing the Population Of Tamsmentioning

confidence: 99%

Tumor-Associated Macrophages as Target for Antitumor Therapy

Sawa-Wejksza

Kandefer‐Szerszeń

2017

Arch. Immunol. Ther. Exp.

176

132

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It is well known that the microenvironment of solid tumors is rich in inflammatory cells that influence tumor growth and development. Macrophages, called tumor-associated macrophages (TAMs), are the most abundant immune cell population present in tumor tissue. Several studies have demonstrated that the density of TAMs is associated with a poor prognosis and positively correlates with tumor growth. Several studies have proved that TAMs may activate and protect tumor stem cells, stimulate their proliferation as well as promote angiogenesis and metastasis. Furthermore, TAMs-derived cytokines and other proteins, such as CCL-17, CCL-22, TGF-β, IL-10, arginase 1, and galectin-3, make a significant contribution to immunosuppression. Since TAMs influence various aspects of cancer progression, there are many attempts to use them as a target for immunotherapy. The numerous studies have shown that the primary tumor growth and the number of metastatic sites can be significantly decreased by decreasing the population of macrophages in tumor tissue, for example, by blocking recruitment of monocytes or eliminating TAMs already present in the tumor tissue. Moreover, there are attempts at reprogramming TAMs into proinflammatory M1 macrophages or neutralizing the protumoral products of TAMs. Another approach uses TAMs for anticancer drug delivery into the tumor environment. In this review, we would like to summarize the clinical and preclinical trials that were focused on macrophages as a target for anticancer therapies.

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Section: Decreasing the Population Of Tamsmentioning

confidence: 99%

Tumor-Associated Macrophages as Target for Antitumor Therapy

Sawa-Wejksza

Kandefer‐Szerszeń

2017

Arch. Immunol. Ther. Exp.

176

132

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“…Clodronate liposomes are commonly used in biomedical research to deplete macrophages to understand their function in vivo. However, the high toxicity of this approach limits the translational relevance of these studies [99,100].…”

Section: Strategies To Deplete Tamsmentioning

confidence: 99%

Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses

Anfray

Ummarino

Andón

et al. 2019

Cells

240

205

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: Established evidence demonstrates that tumor-infiltrating myeloid cells promote rather than stop-cancer progression. Tumor-associated macrophages (TAMs) are abundantly present at tumor sites, and here they support cancer proliferation and distant spreading, as well as contribute to an immune-suppressive milieu. Their pro-tumor activities hamper the response of cancer patients to conventional therapies, such as chemotherapy or radiotherapy, and also to immunotherapies based on checkpoint inhibition. Active research frontlines of the last years have investigated novel therapeutic strategies aimed at depleting TAMs and/or at reprogramming their tumor-promoting effects, with the goal of re-establishing a favorable immunological anti-tumor response within the tumor tissue. In recent years, numerous clinical trials have included pharmacological strategies to target TAMs alone or in combination with other therapies. This review summarizes the past and current knowledge available on experimental tumor models and human clinical studies targeting TAMs for cancer treatment.

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“…Therefore, TAMs might be a potential therapeutic target for cancer treatment strategy in ATC. Indeed, several different experimental approaches have been tried for targeting TAMs: (1) inducing TAMs apoptosis using clodronate loaded liposome [ 27 28 ] or zoledronic acid [ 29 30 ]; (2) inhibiting monocyte differentiation into M2-macrophages using colony stimulating factor 1 receptor inhibitor [ 31 ]; and (3) stimulating repolarization into M1-macrophages using pantoprazole [ 32 ] or IL-12 [ 33 ]. Recently, Passaro et al [ 34 ] demonstrated that oncolytic adenovirus dl922-947 reduced tumor growth and induced repolarization of TAMs into cytotoxic M1-marophages.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Densities Correlated with CXC Chemokine Receptor 4 Expression and Related with Poor Survival in Anaplastic Thyroid Cancer

Kim

et al. 2016

Endocrinol Metab

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BackgroundTumor associated macrophages (TAMs) and CXC chemokine receptor 4 (CXCR4) have emerged as potential biomarkers in various human cancers. The aims of this study were to investigate the clinical characteristics of anaplastic thyroid cancer (ATC) patients according to the TAM numbers in the tumor tissue, and to evaluate the associations between CXCR4 expressions and macrophage densities in ATC tumor microenvironment.MethodsTotal 14 ATC samples from thyroid tissue microarray were used. Immunohistochemical staining was performed using anti-CD163 and anti-CXCR4 antibodies. According to the immunoreactivity of CD163, all subjects were divided into two groups: low-CD163 (n=8) and high-CD163 (n=6) groups.ResultsThe mean diagnostic age was 65±7 years and the median tumor size was 4.3 cm, ranging 2.5 to 15 cm. Clinicopathological characteristics were not significantly different between low-CD163 and high-CD163 groups, while age of diagnosis was younger in high-CD163 group than that of low-CD163 group with marginal significance (56.9±5.5 years vs. 67.5±6.8 years, P=0.09). However, overall survival was significantly reduced in high-CD163 group (5.5 months [range, 1 to 10]) compared with low-CD163 groups (8.8 months [range, 6 to 121); log-rank test, P=0.0443). Moreover, high-CD163 group showed strong CXCR4 expressions in both cancer and stromal compartments, while low-CD163 group showed relatively weak, stromal-dominant CXCR4 expressions. Additionally, CD163 and CXCR4 expressions showed a strong positive correlation (γ2=0.432, P=0.013).ConclusionIncreased number of TAMs showed poor overall survival in ATC, suggesting TAMs are potentially a prognostic biomarker for ATC. CXCR4 expression was significantly correlated with CD163-positive TAM densities, which suggest the possible role of CXCR4 in TAM recruitments.

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A novel liposomal Clodronate depletes tumor-associated macrophages in primary and metastatic melanoma: Anti-angiogenic and anti-tumor effects

Cited by 96 publications

References 43 publications

Tumor-Associated Macrophages as Target for Antitumor Therapy

Tumor-Associated Macrophages as Target for Antitumor Therapy

Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses

Macrophage Densities Correlated with CXC Chemokine Receptor 4 Expression and Related with Poor Survival in Anaplastic Thyroid Cancer

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