Search results for "microenvironment."
showing 10 items of 363 documents
DECORIN EFFECTS ON PROTEOMIC PROFILING OF BREAST CANCER CELLS: AN UPDATED STUDY
2015
The malignant carcinomas are characterized by several capabilities acquired by the neoplastic cells, among which the ability to invade the extracellular matrix (ECM) and to establish a crosstalk with several ECM components. Under this respect, the extracellular microenvironment is an entity extraordinarily rich of information with opposite signals. Our group has long undertaken the study of the effects of ECM molecules on the behavior of cancer cells in vitro. Among the studied molecules, the decorin was found to exert a non-permissive effect on the growth and motility of the transfected tumor cells. The decorin, belongs to the family of small leucine-rich proteoglycans (SLRP) and is involv…
Immune regulation by regulatory T cells: implications for transplantation.
2003
Item does not contain fulltext The induction of antigen-specific T cell tolerance and its maintenance in the periphery are critical for the immune system to prevent autoaggressive immune responses. Our current state of knowledge about the immunoregulatory mechanisms responsible for T cell tolerance in the periphery offers new possibilities for immunomodulation to prevent transplant rejection as well as to diminish autoimmune reaction or chronic allergy. There is growing evidence that dendritic cells, besides their well-known T cell stimulatory functions, also maintain and regulate T cell tolerance in the periphery. This control function is exerted by certain maturation stages and subsets of…
Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects
2022
Immunotherapy is improving the prognosis and survival of cancer patients, but despite encouraging out-comes in different cancers, the majority of tumors are resistant to it, and the immunotherapy combinations are often accompanied by severe side effects. Here, we show that a periodic fasting-mimicking diet (FMD) can act on the tumor microenvironment and increase the efficacy of immunotherapy (anti-PD-L1 and anti-OX40) against the poorly immunogenic triple-negative breast tumors (TNBCs) by expanding early exhausted effector T cells, switching the cancer metabolism from glycolytic to respiratory, and reducing collagen depo-sition. Furthermore, FMD reduces the occurrence of immune-related adve…
Acidic Environment Leads to ROS-Induced MAPK Signaling in Cancer Cells
2011
Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e), pH(i)) and mitogen-activated-protein-kinases (ERK1/2, p38) was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i) in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furth…
p53 Isoform D133p53a: A Novel Transcriptional Enhancer of T-Cell Effector Function to Improve T-Cell Based Cancer Immunotherapy
2018
Abstract Background: Adoptive transfer of genetically modified T lymphocytes with tumor antigen-specific receptor has proven efficacy in cancer immunotherapy. However, in many patients the overall benefit is still limited due to various tumor escape mechanisms. Cell damage and metabolic/hypoxic stress in the tumor microenvironment (TME) can lead to a dysfunctional anti-tumor T cell response called T cell senescence. The tumor suppressor TP53 is a master molecule in the regulation of cell cycle and senescence. Few studies have demonstrated the critical role of p53 isoforms in the regulation of cellular senescence mainly in tumor cells. However, their role in tumor infiltrating lymphocytes (T…
Transmission of Information in Neoplasia by Extracellular Vesicles.
2015
Paracrine interactions among neoplastic and nonneoplastic cells in the immediate tumor microenvironment are important for tumor growth and metastatic spreading. Most of the studies in the past decade addressing these cellular interactions have focused on tumor cell-derived soluble molecules. Recently, these studies and interest have shifted to nanosized extracellular vesicles (EVs) and especially ectosome and exosome-associated molecules [1]. They contain not only proteins, but also lipids, mRNA, and microRNA [1], which can regulate gene expression in their target cells in a much more pleiotropic manner [1]. While exosomes originate by a sequential process of inward budding of late endosome…
Hematologic malignancies: The exosome contribution in tumor progression
2020
Abstract The bone marrow, composed of cells, extracellular matrix, and soluble factors, such as cytokines, chemokines and signaling molecules, provides a favorable microenvironment for hematologic tumor progression and for the development of drug resistance. Recently, extracellular vesicles (EVs), released by tumor and surrounding cells, have emerged as important players within the bone marrow niche. Here we will discuss the current knowledge on the EV- mediated crosstalk between tumor and normal cells, in order to better understand how vesicles can contribute to tumor progression. Advances in the knowledge of the role of cell-derived EVs in tumor microenvironment highlight the possibility …
CCL3 and CCL4, the Major Chemokines Produced by CD38+ Chronic Lymphocytic Leukemia Cells, Facilitate Microenvironmental Interactions of Neoplastic Ce…
2008
Abstract CD38, a negative prognostic marker for patients with CLL, has been demonstrated to be a key molecule in the interactions occurring in the context of tumor microenvironment, mediating both survival and migratory signals for CLL cells. By taking advantage of gene expression profiling studies (GEP) comparing 11 CD38pos (CD38>30%) and 15 CD38neg (CD38<10%) CLLs, we identified as over-expressed in CD38pos CLL cells: i) genes for the two C-C chemokines CCL3 and CCL4 (median-log difference, MLD-CCL3= 3.5; MLD-CCL4=4.4); real-time quantitative PCR (RTQ-PCR) of selected cases confirmed GEP results; ii) the gene for CD49d (MLD=4.4); a high correlation between CD38 and CD49d pro…
Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation
2020
AbstractThe pathophysiology of endometriosis (EM) is an excellent example of immune dysfunction, reminiscent of tumor microenvironment as well. Here, we report that an interplay between C3 and mast cells (MCs) is involved in the pathogenesis of ectopic EM. C3 is at the epicenter of the regulatory feed forward loop, amplifying the inflammatory microenvironment, in which the MCs are protagonists. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse, into the peritoneum of the recipient mice. The wild type mice showed greater amount of…
Targeting cancer stem cells and the tumor microenvironment
2015
Compelling evidence indicates that the survival and behavior of cancer stem cells (CSCs) are positively regulated by specific stimuli received from the tumor microenvironment, which dictates the maintenance of stemness, invasiveness, and protection against drug-induced apoptotic signals. CSCs are per se endowed with multiple treatment resistance capabilities, thus the eradication of CSC pools offers a precious strategy in achieving a long-term cancer remission. Numerous therapies, aimed at eradicating CSCs, have been elaborated such as: (i) selective targeting of CSCs, (ii) modulating their stemness and (iii) influencing the microenvironment. In this context, markers commonly exploited to i…