Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “microenvironment”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources
PubMedDate not supplied

Disparate regulation of human fetal erythropoiesis by the microenvironments of the liver and bone marrow.

The liver and the bone marrow (BM) are the major organs that support hematopoiesis in the human fetus. Although both tissues contain the spectrum of hematopoietic cells, erythropoiesis dominates the liver. Previous studies suggested that a unique responsiveness of fetal burst-forming units erythroid (BFU-E) to erythropoietin (EPO) obviates the need for cytokines with burst-promoting activity (BPA) in fetal erythropoiesis. This potential regulatory mechanism whereby fetal erythropoiesis is enhanced was further investigated. Fluorescence-activated cell sorting was used to isolate liver and BM progenitors based on their levels of CD34 and CD38 expression. The most mature population of CD34+ lineage (Lin-) cells was also the most prevalent of the three subpopulations and contained BFU-E responsive to EPO alone under serum-deprived conditions. Kit ligand (KL) also strongly synergized with EPO in stimulating the growth of these BFU-E. An intermediate subset of CD34++CD38+Lin- cells contained erythroid progenitors responsive to EPO alone, but also displayed synergism between EPO and KL, granulocyte-macrophage colony-stimulating factor (GM-CSF), or interleukin (IL)-3, demonstrating that erythroid progenitors that respond to cytokines with BPA do exist in fetal tissues as in the adult BM. Candidate stem cells (CD34++CD38-Lin- cells) did not respond to EPO. Synergisms among KL, GM-CSF, and IL-3, and to a lesser extent granulocyte colony-stimulating factor (G-CSF) and FLK-2/FLT-3 ligand (FL), supported the growth of primitive multipotent progenitors that became responsive to EPO. These data define the limits of EPO activity in fetal erythropoiesis to cells that express CD38 and demonstrate the potential for various cytokine interactions to be involved in regulating fetal erythropoiesis. Furthermore, a comparison of the responses of liver and BM erythroid progenitors revealed similarity in their responses to cytokines but a difference in the frequency of BFU-E among the three subpopulations examined. A higher frequency of BFU-E among the intermediate and late progenitor subsets in the liver indicates that regulatory factors acting on stem cells and their immediate progeny are partially responsible for the high content of erythropoiesis in the liver. These data implicate a critical role for the microenvironments of the liver and BM in regulating the disparate levels of erythropoiesis in these tissues.

Antigens, CD↗
PubMed1995

Modulation of synaptic transmission at low temperatures by hibernation-related changes in ionic microenvironment in hippocampal slices of golden hamsters.

In hamsters, the entrance into hibernation is associated with a respiratory acidosis and elevation of the blood plasma concentrations of potassium, calcium, and magnesium. To investigate the effects of presumed hibernation-related ionic changes in the brain interstitium on neuronal function, the transmission properties of hippocampal slices prepared from golden hamsters were studied at low temperatures in vitro. Slices were investigated at 15-20 degrees C in artificial cerebrospinal fluid (ACSF) of variable composition (K+, 3-5 mM; Ca2+, 2-4 mM; Mg2+, 2-4 mM; pH 7.0-7.7). Population action potentials (population spikes, PS) of CA1 pyramidal cells were continuously evoked with 100-microseconds stimulus pulses delivered to the Schaffer collaterals/commissural fibers in intervals of 30 s. The PS amplitude was measured as a function of extracellular ion concentrations at given temperatures or as a function of temperature at a given ACSF composition. Elevation of [K+]o, [Mg2+]o, or [H+]o all reduced the PS amplitude at low temperatures, whereas elevation of [Ca2+]o increased the PS amplitude. In conclusion, changes in the ionic microenvironment occurring during entrance into hibernation presumably result in depression of synaptic transmission at low temperatures in the hamster hippocampus. The modulatory effect of ionic changes may be an important factor supporting a general depression of the brain during entrance into hibernation.

Animals↗
PubMed2002

Quantitative analysis of adhesion molecules on cellular constituents of the human uterine microenvironment under the influence of estrogen and progesterone.

The uterus contains all the components of a tertiary lymphoid compartment. We hypothesize that specific leukocyte recruitment to the endometrium during the secretory phase of the menstrual cycle and early pregnancy limits the type of immunocyte that gains access. The present study utilized flow cytometry to define and quantify adhesion molecules possibly used by decidual infiltrating lymphocytes (DIL) as homing receptors, uterine microvascular myometrial endothelial cells (UtMVE-Myo) as addressins, and secretory endometrial stroma cells (STO) as retainment factors. Human umbilical cord vein endothelial cells and peripheral blood lymphocytes were used as control cells for comparison studies. DIL were composed of predominantly lymphocyte function-associated antigen (LFA)-1+, intercellular adhesion molecule (ICAM)-1+, LFA-2+, LFA-3+, gp150,95+, alpha1beta1+, Hermes cell adhesion molecule (H-CAM)+, and neural cell adhesion molecule (N-CAM)+ (CD56(bright)) memory/effector natural killer cells. A significant number of UtMVEC-Myo expressed platelet endothelial cell adhesion molecule (PECAM)-1, a percentage were uniquely LFA-3+, and alpha4 integrin expression was uniquely high. An increased number of STO uniquely expressed alpha3, beta3, and LFA-3, whereas alpha2, alpha4, alphaVbeta3, and H-CAM were significantly increased. Possible unique adhesions of DIL:UtMVEC-Myo included SLe(x):PECAM, vascular cell adhesion molecule-1:alpha4, and LFA-2:LFA-3, whereas DIL:STO included LFA-2:LFA-3 and N-CAM:N-CAM. Unique molecules on DIL may also associate with extracellular matrix (ECM) or complement on UtMVEC-Myo or STO to form gp150,95:fibrinogen/iC3b/C3dg, alpha1beta1:laminin (LM)/collagen (CO), and ICAM-1:fibronectin (FN) interactions. Bridges of ECM may also form between DIL and UtMVEC-Myo adhesion molecules including ICAM-1:FN:ICAM-1 and alpha4beta1:FN:alpha4beta1. DIL:ECM:STO interactions may involve alpha2beta1:CO:alpha2beta1, alpha3beta1:LM/CO/FN:alpha3beta1, alphaVbeta3:VN:alphaVbeta3, and H-CAM:hyaluronate:H-CAM. It is likely that many adhesion molecules play a role in the recruitment and retainment of specialized lymphocytes within the uterine microenvironment. (Mackay et al., 1990).

Adult↗
PubMed1998

Investigation of the Microenvironment in Nonionic Reverse Micelles Using Methyl Orange and Methylene Blue as Absorption Probes

The microenvironment in nonionic reverse micelles of Triton X-100, n-hexanol, and water in cyclohexane is investigated by using methyl orange (MO) and methylene blue (MB) as absorption probes. Information about the states of water in the polar core of the reverse micelles is obtained through the solvatochromic behavior of MO and the sensitivity of the complex formation between MB and Triton X-100 in reverse micelles to the state of water in the polar core. The results obtained from the spectra of MO and MB in the TX-100 reverse micelles with different amounts of water are compatible with the proposal that there are three types of water present in the polar core: the primary bound water, which interacts directly with the ethylene oxide (EO) groups of the surfactant to form a primary hydration shell, the second bound water, which is next to the primary hydration shell of the EO groups and bound less tightly, and the free water, which is present in the water pool and resembles the bulk water. It is found that there is an equilibrium between two states of MB in the reverse micelles: the bound MB and the free MB, and the presence of secondary bound water and free water will lead to the equilibrium shift from bound MB to free MB. In the Triton X-100 reverse micellar system studied, the secondary bound water is present at about W = 1.8 and water pools begin to form when the water content reaches W = 5.3. The strong interaction between MB and nonionic surfactants, which results in the complex formation, and its sensitivity to the state of water in the polar core are found to be also present in the reverse micelles of either Triton X-114 or C12E4 in cyclohexane. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗
PubMed2002

The role of cytokines in the epithelial cancer microenvironment.

The epithelial tumour microenvironment is a complex tissue comprising variable numbers of tumour cells, fibroblasts, endothelial cells and infiltrating leucocytes. Cytokines are key molecules controlling autocrine or paracrine communications within and between these individual cell types. Under some circumstances, endogenous cytokines may orchestrate host responses against the tumour, but there is increasing evidence that the cytokine network contributes to tumour growth, progression and host immuno-suppression. In this review we outline some of the actions of endogenous cytokines in epithelial tumours with particular emphasis on tumour necrosis factor alpha, TNF, related inflammatory cytokines and the chemokine group of chemoattractant cytokines.

Animals↗
PubMed1999

The human thymic microenvironment: new approaches to functional analysis.

Although immunohistological techniques have revealed molecular niches within the human thymic microenvironment, functional analysis is limited by the assay systems available. However, our recent studies using antibody phage display have revealed a high degree of molecular conservation between the microenvironmental molecules of different species. We have therefore isolated single-chain antibodies specific for evolutionarily conserved epitopes, shared by human and mouse, and used these in murine thymic functional assays. The detection of such shared human/rodent molecules makes it possible to functionally 'walk' from mouse to man, providing us with an experimental approach to functional analysis of the human thymus.

Animals↗
PubMed2000

The immunological microenvironment in the CNS: implications on neuronal cell death and survival.

Microenvironmental factors have a profound influence on resident cell populations and their ability to modulate an immune response. The unique central nervous system (CNS) microenvironment has important effects in this regard, resulting in the establishment of immune privilege. The immune response in the CNS is under tight control of bipolar regulatory mechanisms. Neurons have a suppressive potential, which prevents and limits the formation of inflammatory responses. In contrast, activated lymphocytes, which can invade the CNS, deposit potentially pro-inflammatory mediators. The balance between pro- and anti-inflammatory factors determines localization, intensity and course of immune responses in the brain. Thus, an overwhelming invasion of activated lymphocytes, which may have emerged from a recent anti-microbial immune response, may create inflammation in intact parts of the CNS. In contrast, in compromised brain areas, much weaker proinflammatory forces are required to create the same effect. Thus, in degenerative brain lesions, inflammatory infiltrates may be formed easily. Immune cell invasion and expression of immune effector molecules in degenerative CNS disease could exert a variety of actions on the neurons. In the first instance, activation of the local immune response could be harmful to resident brain cells, possibly resulting in neuronal cell death. Alternatively, immune cell-derived mediators could protect and support the regeneration of damaged neurons. Recently, it has been realized that normal inflammatory cells (lymphocytes and macrophages) produce neurotrophic factors. In addition, pro-inflammatory cytokines released by invading immune cells may have a role in neuroprotection. Infiltration of degenerative brain areas by inflammatory cells could thus reflect a beneficial process encouraging neuronal survival and local cell regeneration.

Animals↗
PubMed1986

Immunohistochemical characterization of the thymic microenvironment. A light-microscopic and ultrastructural immunocytochemical study.

The epithelial framework of the human thymus has been studied in parallel by immunohistochemical methods at the light- and electron-microscopic levels. Different monoclonal antibodies were used, reacting with components of the major histocompatibility complex, keratins, thymic hormones and other as yet antigenically undefined substances, which show specific immunoreactivities with human thymus epithelial cells. The electron-microscopic immunocytochemical observations clearly confirm microtopographical differences of epithelial cells not only between the thymic cortex and medulla, but also within the cortex itself. At least four subtypes of epithelial cells could be distinguished: 1) the cortical surface epithelium; 2) the main cortical epithelial cells and thymic nurse cells; 3) the medullary epithelial cells; and 4) the epithelial cells of Hassall's corpuscles. The various epithelial cell types of the thymus display several common features like tonofilaments, desmosomes and some surface antigens as demonstrated by anti-KiM3. In other respects, however, they differ from each other. The cortical subtype of thymic epithelial cells including the thymic nurse cells shows a distinct pattern of surface antigens reacting positively with antibodies against HLA-DR (anti-HLA-DR) and anti-21A62E. Electron-microscopic immunocytochemistry with these antibodies clearly reveals a surface labeling and a narrow contact to cortical thymocytes particularly in the peripheral cortical regions. An alternative staining pattern is realized by antibodies to some antigens associated with other subtypes of thymic epithelial cells. Medullary epithelial cells as well as the cortical surface epithelium react likewise positively with antibodies to special surface antigens (anti-Ep-1), to special epitopes of cytokeratin (anti-IV/82), and to thymic hormones (anti-FTS). The functional significance of distinct microenvironments within the thymus provided by different epithelial cells is discussed in view of the maturation of T-precursor cells.

Antibodies, Monoclonal↗
PubMed1989

Splenic outer periarterial lymphoid sheath (PALS): an immunoproliferative microenvironment constituted by antigen-laden marginal metallophils and ED2-positive macrophages in the rat.

In an attempt to reveal the role of antigen-laden marginal metallophil (MM) and other macrophages in the intrasplenic immune response of a specific B-cell lineage to a thymus-independent type-2 antigen (Ficoll conjugated with fluorescein isothiocyanate), simultaneous immunohistological observations of the involved cells were performed in the rat. By newly established methods of double or triple immunostainings, time-kinetics of the following parameters were studied and compared: (1) the antigen, (2) the specific antibody-forming cells (AFC) directed to the fluorescein-isothiocyanate determinant, (3) proliferating cells labeled with 5-bromo-2'-deoxyuridine (BrdU), and (4) macrophage subpopulations recognized by monoclonal antibodies (ED2 and ED3). The antigen localized stably not only in the marginal-zone macrophages but also in the MM except around the follicular area. The increase of BrdU-positive cells was observed from day 2 up to day 4 after antigen injection mostly in the periphery of the periarterial lymphoid sheath (outer PALS), which indicated antigen-induced proliferation. As a novel finding, the majority of AFC, both BrdU-positive and -negative, were either closely associated with the antigen-laden MM, or forming cell clusters with ED2-positive macrophages in the outer PALS. In contrast, there were very few AFC in juxtaposition to antigen-free MM in the follicular area or the antigen-laden marginal zone macrophages. The results led to the proposal of a hypothesis that the antigen-laden MM together with ED2-positive macrophages constitute an immunoproliferative microenvironment for the plasmacellular reaction by accumulating the antigen-specific B-cell lineage and promoting these cells to differentiate into the AFC and to proliferate in the outer PALS.

Animals↗
PubMed1988

Implantation of cultured thymic fragments in congenitally athymic (nude) rats. Ultrastructural characteristics of the developing microenvironment.

Cultured thymic fragments correspond to the thymic microenvironment depleted of lymphocytes and dendritic cells. When these fragments are implanted under the kidney capsule of congenitally athymic rats, lymphocytes and dendritic cells of host origin enter the graft and induce thymus-dependent immunity in the recipient. This paper describes the ultrastructure of the fragments and the changes that occur during the restoration of normal thymic architecture. At the end of the culture period of 6-9 days and in the early stages after implantation, the grafts consist of keratin-containing epithelial cells of unusual morphology that can be labelled with antibodies raised against the epithelium of the mid/deep cortex and the subcapsule/medulla. Normal thymic architecture develops, including nerves and blood vessels, as lymphocytes populate the environment, and by 4-6 weeks the epithelial cells are the same phenotypically and ultrastructurally as those found in normal rat thymus. However, some areas without lymphocytes still contain the atypical epithelial cells seen before implantation. Large multinucleated giant cells are also present with a few associated epithelial cells of subcapsular/medullary phenotype. In conclusion, the cultured thymic fragments contain a hitherto unknown precursor epithelial cell with an atypical ultrastructure and phenotype that is not seen in normal development.

Animals↗
PubMed1991

Variation in the airborne fungal spore population of the Tuscarawas Valley. II. A comparison of arboreal and nonarboreal microenvironments.

For years the medical profession has recognized a relationship between fungal airspora and the incitement of respiratory allergies. An evaluation of outdoor fungal airspora on an eastern Ohio campus during June 1988 revealed significant differences in quality and quantity with respect to microenvironments. Type of vegetation, diurnal periodicities, and daily weather conditions affected the airspora at each site. Shaded lawns within groves and windbreaks, unshaded lawns, and asphalt-covered parking lots presented varying dynamics for fungal spore liberation. Unshaded lawns produced airspora most abundantly during morning and least abundantly during afternoon. Arboreal sites produced airspora most prolifically at midday. A deciduous sycamore grove produced fewer afternoon airspora than evergreen pine and arborvitae stands. Evening airspora at all vegetated sites increased after experiencing afternoon troughs. Frequently encountered molds included Cladosporium spp., brightly pigmented sterile mycelia, and Alternaria spp.

Air Microbiology↗
PubMed1992

Microenvironment of tryptophan residues in beta-lactoglobulin derivative polypeptide-sodium dodecyl sulfate complexes.

The changes of microenvironment of tryptophan residues in beta-lactoglobulin A and its cyanogen bromide (CNBr) fragments with the binding of sodium dodecyl sulfate (SDS) were studied with measurements of the rates of N-bromosuccinimide (NBS) modification reactions by stopped-flow photometry. Two tryptophan residues of carboxyamidomethylated (RCM) beta-lactoglobulin A in the states of their complexes with SDS were clearly distinguishable by their differences in NBS modification rates. We confirmed by experiments with CNBr fragments containing trytophan residue. The modification rates of Trp 19 in RCM beta-lactoglobulin A-SDS complexes were about 10-fold smaller than those expected for tryptophan residues exposed entirely to the aqueous solvent. The Trp 61 was hardly changed. The change of rate constants for Trp 19 was virtually consistent with those observed when N-acetyl-L-trytophan ethylester was dissolved in SDS micelles. For various species of polypeptide-SDS complexes, all tryptophan residues were reactive to NBS and also, for some of them, the differences in NBS modification rates were observed between tryptophan residues on a common polypeptide chain. These results suggest micellar and heterogeneous bindings of SDS to polypeptides.

Cyanogen Bromide↗
PubMed1978

[Regulation of the human erythropoietic proliferation pool by the microenvironment (author's transl)].

The Effects of Various Substances in the Culture Microenvironment on the Proliferation of Erythroblasts in vitro were Studied and Evaluated by differential cell and mitosis counting in normal and pathologic bone marrow. The mitotic frequency and maturation correlated directly with the erythropoietin content of the medium and were potentiated on addition of either folic acid, etiocholanolon or cAMP. However, erythroblast proliferation was stimulated independently of erythropoietin concentration when either cobalt, and androgen or an anabolic substance was added to the medium. An iron-deficient medium prevented the maturation of erythroblasts to reticulocytes, thereby rendering erythropoiesis ineffective. The existence of an erythrocyte chalone ineffective. The existence of an erythrocyte chalone or an erythropoietin inhibitor could not be deduced from our experiments since the transformation of pluripotent to erythropoetin-sensitive stem cells is not included. A stimulation of the granulopoietic proliferation pool occurred when serum from patients with either polycythemia vera or after acute blood loss was added to the medium.

Androgens↗
PubMed1990

Sugar receptors of the stromal cell layer in human long-term bone marrow cultures: their presence, modulatory responses to changes in the microenvironment and potential role in cellular adhesion.

Intimate cellular contacts and coordinated supply of regulatory factors are required to maintain the still inexplicable dynamic equilibrium of hemopoiesis. To infer the potential participation of protein-carbohydrate interaction in this complex process, human long-term bone marrow cultures were initiated from eleven donors, and the adherent cell layer was characterized enzyme- and immunohistochemically. Utilizing an array of carrier-immobilized carbohydrate ligands and sulfated polysaccharides as probes, specific binding of various constituents of the carbohydrate chains of cellular glycoconjugates to the stromal cells was unmistakably disclosed. Biochemical analysis, employing glycocytologically effective ligands in affinity chromatography, corroborated this result. The extent of binding was markedly lower in the two samples, derived from leukemia patients. Pronounced adaptive responses for this characteristic followed changes in the culture microenvironment that are known to influence qualitative and quantitative aspects of hemopoiesis in vitro, namely omission of hydrocortisone and horse serum or addition of cytokines. Similarly, such adaptive modulation occurred on the level of accessible cell surface receptors, monitored by neoglycoenzymes. These binding sites can be involved in mediation of cellular interactions, as revealed in a model system by the interference of N-acetyl-D-galactosamine in cell adhesion. Overall, the results support the idea that glycobiological recognition may contribute to the functional integrity of the stromal cell layer as well as provide the basis for further analysis.

Bone Marrow↗
PubMed1991

Evidence for the disruption of the bone marrow microenvironment by combined exposures to inhaled benzene and ingested ethanol.

Studies have been performed to investigate the effects of combined in vivo exposures to inhaled benzene and ingested ethanol on the earliest known murine erythropoietic precursor cells, the Burst Forming Unit--Erythroid (BFU-E) and the Colony Forming Unit--Erythroid (CFU-E). Previously we had determined that murine erythropoietic cell populations were particularly susceptible to combined benzene + ethanol treatments. The most striking example of erythropoietic disruption was the transient appearance of large numbers of nucleated red cells (normoblasts) in the circulating blood. In the present studies, male C57Bl/6 mice were exposed to 300 ppm benzene via inhalation for 6 h/d x 5 d/wk x 9 wks. Groups of mice were also exposed to 5% ethanol in the drinking water 4 d/wk x 9 wks. Appropriate controls were also maintained. The hematological assays were performed after 1, 4, and 9 weeks of exposure. After 4 weeks of exposure large numbers of normoblasts appeared in the circulating blood of mice exposed to benzene + ethanol. However, there were no corresponding increases in the numbers of the earliest erythroid progenitor cells in the bone marrow. There were, however, marked increases in the numbers of these cells in the spleen. Previous work in this laboratory had confirmed that the marrow was the source of circulating normoblasts among animals exposed to benzene + ethanol. We conclude, therefore, that circulating normoblasts appear in the peripheral blood because of changes in the bone marrow microenvironment rather than as a consequence of increased erythropoietic proliferation in the marrow.

Administration, Inhalation↗
PubMed1988

Microenvironment of thymic myoid cells in myasthenia gravis.

The microenvironment of myoid cells (MyCs) was studied in myasthenia gravis (MG) thymitis with lymphoid follicular hyperplasia (LFH) (nine cases) and with diffuse B cell infiltration (one case), and compared with findings in the thymuses of non-myasthenic control subjects (ten cases). Double immunostaining was used to demonstrate MyCs labelled by anti-desmin together with other thymic components such as keratin-positive epithelial cells, Ki-M 1-positive interdigitating reticulum cells (IDCs), Ki-M 4-positive follicular dendritic reticulum cells, Ki-M 6-positive macrophages, CD22-positive B-cells, CD1-positive cells, CD3-positive T-cells or HLA-DR-positive cells. Round or elongated MyCs were confined to the thymic medulla and were surrounded by CD3-positive T-cells and CD22-positive B-cells. In MG thymitis MyCs were localized in the vicinity of, but not inside germinal centres (GCs). MyCs were always HLA-DR-negative, but were invariably embedded in a cellular micromilieu with strong HLA-DR expression. A remarkable feature of MG thymitis was that the great majority of MyCs were in intimate contact with intramedullary IDCs. Morphometric studies confirmed that such contacts were significantly less frequent in thymuses from non-myasthenic subjects. This indicates that an IDC-dependent antigen-presenting process for T-cells may actively involve MyCs in MG thymitis.

Adolescent↗
PubMed2006

Mechanisms of tumor escape: role of tumor microenvironment in inducing apoptosis of cytolytic effector cells.

Spontaneous tumors grow and kill the host unless therapy reduces their mass to a level where the immune system, it is thought, can control their growth and diffusion. Indeed, in many instances tumors can reappear, become resistant to therapy, and escape the host immune response. Many mechanisms of tumor escape operating in the tumor microenvironment have been proposed: 1) low or absent expression of molecules on tumor cells involved in tumor target cell recognition; 2) absence of co-stimulation leading to tolerization of T cells; 3) soluble factors secreted by tumor cells inhibiting T cell response; and 4) regulatory T cells, myeloid suppressor cells, and stromal cells may impair immune-cell responses to tumors. Furthermore, tumors can release soluble molecules such as HLA-I (sHLA-I). This, in turn, reduces T cell-mediated immune response and induces apoptosis of cytolytic effector cells such as natural killer and CD8(+) T lymphocytes through the engagement of HLA-I receptors such as CD8 and/or activating isoforms of the inhibitory receptor superfamily. The release of soluble ligand for activating receptors, e.g. UL16 binding proteins and/or MHC class I-related proteins A and B, the natural ligands of NKG2D, may impair activation, effector cell-mediated recognition, and cytolysis of tumor cells. Furthermore, the elimination of anti-tumor effector cells may be achieved by induction of apoptosis consequent to triggering elicited via activating molecules, such as receptors responsible for natural cytotoxicity, upon their binding with ligands expressed on tumor cells.

Animals↗