Myeloid-Derived Suppressor Cells as Osteoclast Progenitors: A Novel Target for Controlling Osteolytic Bone Metastasis

Sawant, Anandi; Ponnazhagan, Selvarangan

doi:10.1158/0008-5472.can-13-0305

Cited by 72 publications

(61 citation statements)

References 23 publications

(40 reference statements)

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“…Recently, MDSCs have been suggested to be precursors of osteoclasts under tumor environment (49,50). Considering that osteopontin is a main component of the bone microenvironment (39), osteopontin might induce the proliferation of LK cells and subsequently expand the MDSCs that may serve as precursors of osteoclasts in the bone.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Derived Osteopontin Suppresses Antitumor Immunity by Promoting Extramedullary Myelopoiesis

et al. 2014

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Extramedullary myelopoiesis occurs commonly in tumor-bearing animals and is known to lead to accumulation of peripheral myeloid-derived suppressor cells (MDSC), which play an important role in immune escape. However, the cellular and molecular mechanisms by which tumors induce extramedullary myelopoiesis are poorly understood. In this study, we found that osteopontin expressed by tumor cells enhances extramedullary myelopoiesis in a CD44-dependent manner through the Erk1/2-MAPK pathway. Osteopontin-mediated extramedullary myelopoiesis was directly associated with increased MDSCs in tumorbearing hosts. More importantly, osteopontin silencing in tumor cells delayed both tumor growth and extramedullary myelopoiesis, while the same treatment did not affect tumor growth in vitro. Finally, treatment with an antibody against osteopontin inhibited tumor growth and synergized with cell-based immunotherapeutic vaccines in mediating antitumor immunity. Our findings unveil a novel immunosuppressive role for tumor-derived osteopontin and offer a rationale for its therapeutic targeting in cancer treatment. Cancer Res; 74(22); 6705-16. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

Tumor-Derived Osteopontin Suppresses Antitumor Immunity by Promoting Extramedullary Myelopoiesis

et al. 2014

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“…Interestingly, only MDSCs from tumors known to metastasize to the bone were able to differentiate into osteoclasts, and only when metastatic lesions were present, suggesting that coordinated signals from the bone marrow and bone metastasis are driving the differentiation of MDSCs into osteoclasts. 70 …”

Section: Mdscs and Pre-metastatic Niches: Beyond Immunosuppressionmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in Cancer: Therapeutic, Predictive, and Prognostic Implications

Díaz-Montero

Finke

Montero

2014

Seminars in Oncology

149

107

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Immune evasion is a hallmark of cancer. While, there are multiple different mechanisms that cancer cells employ, myeloid deriver suppressor cells (MDSCs) are one of the key drivers of tumor mediated immune evasion. MDSCs begin as myeloid cells recruited to the tumor microenvironment where they are transformed into potent immunosuppressive cells. Our understanding of the clinical relevance of MDSCs in cancer patients, however has significantly lagged behind the preclinical literature in part due to the absence of a cognate molecule present in mice, as well as the considerable heterogeneity of MDSCs. However, if one evaluates the clinical literature through the filter of clinically robust endpoints, such as overall survival, three important phenotypes have emerged: promyelocytic, monocytic, and granulocytic. Based on these studies, MDSCs have clear prognostic importance in multiple solid tumors, and emerging data supports the utility of circulating MDSCs as a predictive marker for cancer immunotherapy, and even as an early leading marker for predicting clinical response to systemic chemotherapy in patients with advanced solid tumors. More recent preclinical data in immunosuppressed murine models suggest that MDSCs play an important role in tumor progression and the metastatic process that is independent of their immunosuppressive properties. Consequently, targeting MDSCs either in combination with cancer immunotherapy or independently as part of an approach to inhibit the metastatic process, appears to be a very clinically promising strategy. We review different approaches to target MDSCs that could potentially be tested in future clinical trials in cancer patients.

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“…Infiltration of immunosuppressive myeloidderived suppressor cells inhibits host antitumor immune responses and promotes tumor growth. In skeletal metastasis, myeloid-derived suppressor cells act as osteoclast progenitors, further increasing tumor-induced osteolysis (88), an effect that has been attributed to signals derived from the tumor and the host milieu (89).…”

Section: Immune Systemmentioning

confidence: 99%

Bone Metastases in Lung Cancer. Potential Novel Approaches to Therapy

Vicent

Perurena²,

Govindan

et al. 2015

Am J Respir Crit Care Med

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The skeleton is a common site of metastases in lung cancer, an event associated with significant morbidities and poor outcomes. Current antiresorptive therapies provide limited benefit, and novel strategies of prevention and treatment are urgently needed. This review summarizes the latest advances and new perspectives on emerging experimental and clinical approaches to block this deleterious process. Progress propelled by preclinical models has led to a deeper understanding on the complex interplay of tumor cells in the osseous milieu, unveiling potential new targets for drug development. Improvements in early diagnosis through the use of sophisticated imaging techniques with bone serum biomarkers are also discussed in the context of identifying patients at risk and monitoring disease progression during the course of treatment.

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Myeloid-Derived Suppressor Cells as Osteoclast Progenitors: A Novel Target for Controlling Osteolytic Bone Metastasis

Cited by 72 publications

References 23 publications

Tumor-Derived Osteopontin Suppresses Antitumor Immunity by Promoting Extramedullary Myelopoiesis

Tumor-Derived Osteopontin Suppresses Antitumor Immunity by Promoting Extramedullary Myelopoiesis

Myeloid-Derived Suppressor Cells in Cancer: Therapeutic, Predictive, and Prognostic Implications

Bone Metastases in Lung Cancer. Potential Novel Approaches to Therapy

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