Given its state of stable proliferative inhibition, cellular senescence is primarily depicted as a critical mechanism by which organisms delay the progression of carcinogenesis. Cells undergoing senescence are often associated with the alteration of a series of specific features and functions, such as metabolic shifts, stemness induction, and microenvironment remodeling. However, recent research has revealed more complexity associated with senescence, including adverse effects on both physiological and pathological processes. How organisms evade these harmful consequences and survive has become an urgent research issue. Several therapeutic strategies targeting senescence, including senolytics, senomorphics, immunotherapy, and function restoration, have achieved initial success in certain scenarios. In this review, we describe in detail the characteristic changes associated with cellular senescence and summarize currently available countermeasures.
Humans ; Cellular Senescence ; Carcinogenesis ; Immunotherapy ; Aging ; Tumor Microenvironment

The interactions between B7 molecules and CD28-family receptors are crucial in the regulation of adaptive cellular immunity. In cancer, the aberrant expression of co-inhibitory B7 molecules has been attributed to reduced anti-tumor immunity and cancer immune evasion, prompting the development of cancer therapeutics that can restore T cell function. Murine tumor models have provided significant support for the targeting of multiple immune checkpoints involving CTLA-4, PD-1, ICOS, B7-H3 and B7-H4 during tumor growth, and clinical studies investigating the therapeutic effects of CTLA-4 and PD-1 blockade have shown exceptionally promising results in patients with advanced melanoma and other cancers. The expression pattern of co-inhibitory B7 ligands in the tumor microenvironment has also been largely correlated with poor patient prognosis, and recent evidence suggests that the presence of several B7 molecules may predict the responsiveness of immunotherapies that rely on pre-existing tumor-associated immune responses. While monotherapies blocking T cell co-inhibition have beneficial effects in reducing tumor burden, combinatorial immunotherapy targeting multiple immune checkpoints involved in various stages of the anti-tumor response has led to the most substantial impact on tumor reduction. In this review, we will examine the contributions of B7- and CD28-family members in the context of cancer development, and discuss the implications of current human findings in cancer immunotherapy.
B7 Antigens ; Humans ; Immune Evasion ; Immunity, Cellular ; Immunotherapy* ; Ligands ; Melanoma ; Prognosis ; Tumor Burden ; Tumor Microenvironment

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.
Classification ; Genome ; Herpesvirus 4, Human ; Humans ; Immunity, Cellular ; Prognosis ; Stomach Neoplasms ; Tumor Microenvironment

OBJECTIVETo imitate tumor microenvironment in vivo through construction of two-layer cell spheroid as a three-dimensional tumor model, and to validate its application in the study of Cx43 expression in colorectal cancer cell-fibroblast interactions and colorectal cancer progression.

METHODSThe two-layer cell spheroid was constructed from SW620 colorectal cancer cells and HELF fibroblasts. The expression of Cx43 in the spheroid was detected by immunocytochemistry. The expression of Cx43 in cultured SW620 cells with or without co-cultured fibroblasts was detected by immunocytochemistry and immunofluorescence. The expression of Cx43 in colorectal cancer tissue was detected by immunohistochemistry.

RESULTSThe spheroid showed well-defined cellular morphology and clear boundary between two cell lines.Significant expression of Cx43 was found along the boundary.SW620 cells had no expression of Cx43 when cultured alone, while the expression of Cx43 was induced upon co-culturing with fibroblasts.In the colorectal cancer tissue, expression of Cx43 was minimal in the centre of tumor in contrast to an upregulated expression at invasive front.

CONCLUSIONSThe two-layer cell spheroid is an observable and sensitive model for cell-cell interaction for studies of tumor microenvironment.It can simulate colorectal cancer cell-fibroblast interactions through up-regulation of Cx43 expression.

Cell Communication ; Cell Line, Tumor ; Coculture Techniques ; Colorectal Neoplasms ; metabolism ; pathology ; Connexin 43 ; metabolism ; Fibroblasts ; cytology ; Humans ; Spheroids, Cellular ; cytology ; metabolism ; Tumor Microenvironment ; Up-Regulation

Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease characterized by pulmonary interstitial fibrosis and pulmonary dysfunction.Cell microenvironment is mainly composed of cell components,extracellular matrix,extracellular regulators,and liquid substances.Changes in microenvironment components are closely related to IPF.This article elaborates the roles of cell microenvironments including cytokines,mesenchymal cells,extracellular matrix,and unfolded proteins in the pathogenesis of IPF.
Cellular Microenvironment ; Extracellular Matrix ; Humans ; Idiopathic Pulmonary Fibrosis ; Lung

Cellular Microenvironment ; Endothelial Cells ; cytology ; Hematopoietic Stem Cells ; cytology

Myelodysplastic syndromes (MDS) are hematopoietic malignancies characterized by peripheral cytopenia and dysplastic bone marrow that arise from mutations in the hematopoietic stem/progenitor cells (HSPC). Recently, significant effects have been made to develop appropriate mouse models to study this complex disease. Three general approaches have been used to establish the MDS mouse, including treatment with mutagens or carcinogen, xenotransplantation of human MDS cells, and genetic engineering of mouse hematopoietic cells. In this review, several MDS mouse models and the advances of study on the mechanisms of malignant clone and the marrow microenvironment are summarized. In addition, the progress in xenotransplantation models of MDS and the problems to be solved are discussed briefly.
Animals ; Cellular Microenvironment ; Disease Models, Animal ; Mice ; Myelodysplastic Syndromes

BACKGROUND/OBJECTIVES: Obesity is a risk factor of breast cancer in postmenopausal women. Estrogen deprivation has been suggested to cause alteration of lipid metabolism thereby creating a cellular microenvironment favoring tumor growth. The aim of this study is to investigate the effects of estrogen depletion in combination with excess energy supply on breast tumor development. MATERIALS/METHODS: Ovariectomized (OVX) or sham-operated C3H/HeN mice at 4 wks were provided with either a normal diet or a high-fat diet (HD) for 16 weeks. Breast tumors were induced by administration of 7,12-dimethylbenz(a)anthracene once a week for six consecutive weeks. RESULTS: Study results showed higher serum concentrations of free fatty acids and insulin in the OVX+HD group compared to other groups. The average tumor volume was significantly larger in OVX+HD animals than in other groups. Expressions of mammary tumor insulin receptor and mammalian target of rapamycin proteins as well as the ratio of pAKT/AKT were significantly increased, while pAMPK/AMPK was decreased in OVX+HD animals compared to the sham-operated groups. Higher relative expression of liver fatty acid synthase mRNA was observed in OVX+HD mice compared with other groups. CONCLUSIONS: These results suggest that excess energy supply affects the accelerated mammary tumor growth in estrogen deprived mice.
Animals ; Breast Neoplasms ; Cellular Microenvironment ; Diet ; Diet, High-Fat ; Estrogens* ; Fatty Acids, Nonesterified ; Female ; Humans ; Insulin ; Lipid Metabolism ; Liver ; Mice* ; Obesity ; Postmenopause ; Receptor, Insulin ; Risk Factors ; RNA, Messenger ; TOR Serine-Threonine Kinases ; Tumor Burden

Microfluidic chip is a novel technology platform, in which microchannels are fabricated in different materials. The ability to precisely control the microflows makes it possible to mimic the microenvironment of cells in physiological or pathological states, which provides many distinct advantages for cell research. In this paper are reviewed the design and fabrication of microfluidic chip, the application of microfluidic chip in cell culture and cell researches; the enormous advantages of microfluidic chips in precise experimental control of the cellular microenvironment are introduced.
Cell Adhesion ; Cell Culture Techniques ; Cell Movement ; Cells, Cultured ; Cellular Microenvironment ; Humans ; Microfluidic Analytical Techniques ; methods

Cellular Microenvironment ; Humans ; Myocardial Infarction ; metabolism ; rho-Associated Kinases ; metabolism ; rhoA GTP-Binding Protein ; metabolism