Search results for "Tumor microenvironment."

Immune Control in Hepatocellular Carcinoma Development and Progression: Role of Stromal Cells

2014

Immune control of hepatocellular carcinoma (HCC) is executed by effector immune cells, which efficiently eliminate malignant transformed cells. However, progression of HCC clearly documents failure of tumor immune control, which led to the concept of immune subversion by the tumor environment. Particularly tumor-associated stromal cells cooperate within an inflammatory network, which is responsible for immune privilege. The stromal cell composition matures during tumor growth and is derived from surrounding noncancerous tissue or from circulating cells recruited to the tumor site. Therefore, immunosuppressive stromal cells represent heterogeneous cell lineages, including myeloid cells, lymp…

CCL27 Signaling in the Tumor Microenvironment

2021

Chemokines are a group of small proteins which play an important role in leukocyte migration and invasion. They are also involved in the cellular proliferation and migration of tumor cells.Chemokine CCL27 (cutaneous T cell-attracting chemokine, CTACK) is mainly expressed by keratinocytes of the normal epidermis. It is well known that this chemokine plays an important role in several inflammatory diseases of the skin, such as atopic dermatitis, contact dermatitis, and psoriasis. Moreover, several studies have shown an association between CCL27 expression and a variety of neoplasms including skin cancer.In this chapter, we address the role of chemokine CCL27 in the tumor microenvironment in t…

ROLE OF EXOSOMES RELEASED BY CHRONIC MYELOGENOUS LEUKEMIA CELLS IN THE CROSS-TALK WITH ENDOTHELIAL CELLS

2016

Unraveling the extracellular matrix-tumor cell interactions to aid better targeted therapies for neuroblastoma

2021

Treatment in children with high-risk neuroblastoma remains largely unsuccessful due to the development of metastases and drug resistance. The biological complexity of these tumors and their microenvironment represent one of the many challenges to face. Matrix glycoproteins such as vitronectin act as bridge elements between extracellular matrix and tumor cells and can promote tumor cell spreading. In this study, we established through a clinical cohort and preclinical models that the interaction of vitronectin and its ligands, such as αv integrins, are related to the stiffness of the extracellular matrix in high-risk neuroblastoma. These marked alterations found in the matrix led us to speci…

Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia

2021

BackgroundT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a poor cure rate for relapsed/resistant patients. Due to the lack of T-cell restricted targetable antigens, effective immune-therapeutics are not presently available and the treatment of chemo-refractory T-ALL is still an unmet clinical need. To develop novel immune-therapy for T-ALL, we generated an afucosylated monoclonal antibody (mAb) (ahuUMG1) and two different bispecific T-cell engagers (BTCEs) against UMG1, a unique CD43-epitope highly and selectively expressed by T-ALL cells from pediatric and adult patients.MethodsUMG1 expression was assessed by immunohistochemistry (IHC) on a wide panel of normal t…

γδ T cell-based anticancer immunotherapy: Progress and possibilities

2015

Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activa…

2020

Rationale: Loss of histone macroH2A1 induces appearance of cancer stem cells (CSCs)-like cells in hepatocellular carcinoma (HCC). How CSCs interact with the tumor microenvironment and the adaptive immune system is unclear. Methods: We screened aggressive human HCC for macroH2A1 and CD44 CSC marker expression. We also knocked down (KD) macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. Results: Human HCC showed low macroH2A1 and high CD44 expression compared to control tissues. MacroH2A1 KD CSC-like cells transferred paracrinally their chemoresistant properties to parental HCC cells. MacroH2A1 KD conditioned media transcriptionally reprogrammed parental …

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

2020

AbstractGut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microb…

Role of the protein C receptor in cancer progression

2014

The hemostatic system plays pleiotropic roles in cancer progression by shaping the tumor microenvironment and metastatic niches through thrombin-dependent fibrin deposition and platelet activation. Expanding experimental evidence implicates coagulation protease receptors expressed by tumor cells as additional players that directly influence tumor biology. Pro-angiogenic G protein-coupled signaling of TF through protease activated receptor 2 and regulation of tumor cell and vascular integrins through ligation by alternative spliced TF are established pathways driving tumor progression. Our recent work shows that the endothelial protein C receptor (EPCR), a stem cell marker in hematopoietic, …

Lactate adversely affects the in vitro formation of endothelial cell tubular structures through the action of TGF-beta1.

2006

When lactate accumulation in a tumor microenvironment reaches an average concentration of 10-20 mM, it tends to reflect a high degree of malignancy. However, the hypothesis that tumor-derived lactate has a number of partially adverse biological effects on malignant and tumor-associated host cells requires further evidence. The present study attempted to evaluate the impact of lactate on the process of angiogenesis, in particular on the formation of tubular structures. The endothelial cell (EC) network in desmoplastic breast tumors is primarily located in areas of reactive fibroblastic stroma. We employed a fibroblast-endothelial cell co-culture model as in vitro angiogenesis system normally…