Endostatin inhibits the growth and migration of 4T1 mouse breast cancer cells by skewing macrophage polarity toward the M1 phenotype

Abstract The phenotypic diversity of tumor-associated macrophages (TAMs) increases with tumor development. One of the hallmarks of malignancy is the polarization of TAMs from a pro-immune (M1) phenotype to an immunosuppressive (M2) phenotype. However, the molecular basis of this process is still unclear. Endostatin is a powerful inhibitor of angiogenesis capable of suppressing tumor growth and metastasis. Here, we demonstrate that endostatin induces RAW264.7 cell polarization toward the M1 phenotype in vitro. Endostatin has no effect on TAM numbers in vivo, but results in an increased proportion of F4/80+Nos2+ cells and a decreased proportion of F4/80+CD206+ cells. Overexpression of endostatin in RAW264.7 cells resulted in a decrease in the phosphorylation of STAT3, an increase in expression of vascular endothelial growth factor A and placental growth factor, and an increase in the phosphorylation of STAT1, IκBα and p65 proteins compared with controls. These results indicate that endostatin regulates macrophage polarization, promoting the M1 phenotype by targeting NF-κB and STAT signaling.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

Related Links:

In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Cao X, Xu J Abstract Inflammation has long been proven to engage in tumor initiation and progression. Inflammasome, as a member of innate immunity-induced host defense inflammation, also plays critical roles in cancer. Inflammasome is a multiprotein complex responding to pathogen-associated molecular patterns and damage-associated molecular patterns. It is composed of receptors such as NOD-like receptors and AIM2-like receptors, adaptor protein ASC, and effector caspase-1, which can process proinflammatory cytokines interleukin (IL)-1β and IL-18. It has been reported that upregulated inflammasome acti...
Source: Tumori - Category: Cancer & Oncology Tags: Tumori Source Type: research
Cancer immunotherapy has been heralded as a breakthrough cancer treatment demonstrating tremendous success in improving tumor responses and survival of patients with hematological cancers and solid tumors. This novel promising treatment approach has in particular triggered optimism for triple negative breast cancer (TNBC) treatment, a subtype of breast cancer with distinct clinical features and poor clinical outcome. In early 2019, the FDA granted the first approval of immune checkpoint therapy, targeting PD-L1 (Atezolizumab) in combination with chemotherapy for the treatment of patients with locally advanced or metastatic...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionThe new HSV-1 based platform described provides a potent and versatile approach to developing new oncolytic immunotherapies for clinical use. Each of the modifications employed was demonstrated to aid in optimizing the potential of the virus to both directly kill tumors and to lead to systemic therapeutic benefit. For clinical use, these viruses are expected to be most effective in combination with other anti-cancer agents, in particular PD1/L1-targeted immune checkpoint blockade. The first virus from this program (expressing GALV-GP-R− and hGM-CSF) has entered clinical development alone and in combination ...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
AbstractBreast cancer is no longer considered a single disease, and with better understanding of cancer biology, its management has evolved over the years, into a complex individualized use of therapeutics based on variable expressions of predictive and prognostic factors. With the advent of molecular and genetic research, the complexity and diversity of breast cancer cells and their ability to survive and develop resistance to treatment strategies became more evident. At the same time, targeted therapies evolved, as specific targets were discovered such as HER2 receptor, and androgen receptor. More recent is the developme...
Source: Indian Journal of Surgical Oncology - Category: Cancer & Oncology Source Type: research
This study aims to determine programmed death-ligand 1 (PD-L1) expression and methylation status of PD-L1 promoter in primary tumor tissue and metastatic foci of patients with stage IV breast cancer. Clinicopathological data and survival rates of 57 breast cancer patients, who were initially staged IV, and operated for intact tumors, were retrospectively analyzed. Immunohistochemical analysis of PD-L1 using 57 primary tumors, 33 paired metastatic lymph nodes, and 14 paired distant metastases was performed. Additionally, the methylation rate of the PD-L1 gene promoter region was determined with real-time polymerase chain r...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
CONCLUSION: Cellular immune responses against cancer-germline genes are indicative of appropriateness of these genes as therapeutic targets. PMID: 31356200 [PubMed - as supplied by publisher]
Source: Human Antibodies - Category: Biochemistry Tags: Hum Antibodies Source Type: research
In this study, we investigated local (tumor) and peripheral (blood) cellular immunome of patients with melanoma, breast cancer and brain cancer using a rapid and reliable standardized, multiparameter flow cytometry assay. We used this approach to monitor changes in the peripheral cellular immunome in women with breast cancer undergoing SOC therapy. Our analysis is unique because it is conducted using matched fresh tumor tissue and blood from patients in real-time, within 2-3 hours of sample acquisition, and provides insight into the innate and adaptive immune cell profile in blood and tumor. Specific to blood, this approac...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Myal Breast cancer affects millions of women worldwide, leading to many deaths and significant economic burden. Although there are numerous treatment options available, the huge potentials of immunotherapy in the management of localized and metastatic breast cancer is currently being explored. However, there are significant gaps in understanding the complex interactions between the immune system and breast cancer. The immune system can be pro-tumorigenic and anti-tumorigenic depending on the cells involved and the conditions of the tumor microenvironment. In this review, we discuss current knowledge of breast cance...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
CONCLUSION: These data showed that ctDNA evaluation is a feasible, sensitive and specific biomarker for diagnosis and differential diagnosis of early-stage breast cancer who need chemotherapy. PMID: 31350313 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
More News: Allergy & Immunology | Breast Cancer | Cancer | Cancer & Oncology | Immunotherapy