http://aiocm.org/member/Immunity,%20Inflammation,%20and%20Cancer.pdf

Immunity, Inflammation, and Cancer

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand during cancer, inflammation and infection, and that have a remarkable ability to suppress T-cell responses. These cells constitute a unique component of the immune system that regulates immune responses in healthy individuals and in the context of various diseases. In this Review, we discuss the origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit.

/pdf/myeloid-derived-suppressor-cells-as-regulators-of-the-immune-4w2mvge6zg.pdf

Myeloid-derived suppressor cells as regulators of the immune system.

Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion

Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.

/pdf/microenvironmental-regulation-of-metastasis-49v9l5nr6y.pdf

Microenvironmental regulation of metastasis

TGFβ in Cancer

Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis

http://basicmed.med.ncku.edu.tw/admin/up_img/970307-1.pdf

Abrogation of TGFβ signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis

The role of cell adhesion molecules (CAMs), such as intercellular cell adhesion molecule-1 (ICAM-1), vascular endothelial cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin, has been studied extensively in the process of inflammation. These molecules are responsible for recruiting leukocytes onto the vascular endothelium before extravasation to the injured tissues. Some circulating cancer cells have been shown to extravasate to a secondary site using a process similar to inflammatory cells. The most studied ligands for CAMs expressed on cancer cells, sialyl Lewis (a/x) antigens, are shown to be involved in adhesion to endothelial cells by binding to E-selectin. This process, shared by inflammatory cells and cancer cells, may partially explain the link between inflammation and tumorigenesis. Furthermore, this process may elucidate the therapeutic benefit of anti-inflammatory drugs in cancer treatment. The complexity of the tumor microenvironment has been revealed in the past decade. Currently, intense investigation is aimed at various aspects of the tumor microenvironment in addition to the tumor cells themselves. Here, we review the role of CAMs in extravasation of circulating cancer cells, a key step in metastasis.

Endothelial Cell Adhesion Molecules and Cancer Progression

Expansion and functions of myeloid-derived suppressor cells in the tumor microenvironment.

Objective

In a previous study, we demonstrated that Tie2 regulates angiogenesis in arthritis. The current study was performed to determine whether systemic delivery of a soluble Tie2 receptor (ExTek) using an adenoviral vector (AdExTek) as a Tie2 inhibitor affects arthritis development and progression in an animal model.



Methods

We used a collagen-induced arthritis (CIA) mouse model to study the outcome of treatment with either AdExTek or a control vector. The onset, incidence, and severity of arthritis were quantified. Immunohistologic analysis of endothelium obtained from the paws was performed. Bone destruction in paws was analyzed using phase-contrast radiography.



Results

The data showed that systemic delivery of ExTek before disease development significantly inhibited the onset, incidence, and severity of arthritis. When AdExTek was given after disease onset, the severity of disease in mice treated with AdExTek was significantly lower than that in the control group at 35 days postimmunization, which correlated with significantly diminished angiogenesis in mouse paws. Strikingly, AdExTek treatment protected bone from erosion in the CIA model and reduced levels of RANKL. No differences in collagen-specific antibodies were detected between these 2 groups.



Conclusion

We demonstrated that blocking Tie2 receptor activation inhibits angiogenesis and arthritis development and protects against bone destruction in a CIA mouse model. These findings identify Tie2 as a therapeutic target for arthritis treatment and imply that interventions designed to target the Tie2 pathway could be clinically beneficial.

P. Charles Lin

Papers

Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis

Abrogation of TGFβ signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis

Endothelial Cell Adhesion Molecules and Cancer Progression

Expansion and functions of myeloid-derived suppressor cells in the tumor microenvironment.

Gene therapy targeting the Tie2 function ameliorates collagen-induced arthritis and protects against bone destruction.