The goals of the study were to elucidate the immune mechanisms that contribute to desirable complete remissions of murine colon tumors treated with single radiation dose of 30 Gy. This dose is at the ...upper end of the ablative range used clinically to treat advanced or metastatic colorectal, liver, and non-small cell lung tumors.
Changes in the tumor immune microenvironment of single tumor nodules exposed to radiation were studied using 21-day (>1 cm in diameter) CT26 and MC38 colon tumors. These are well-characterized weakly immunogenic tumors.
We found that the high-dose radiation transformed the immunosuppressive tumor microenvironment resulting in an intense CD8(+) T-cell tumor infiltrate, and a loss of myeloid-derived suppressor cells (MDSC). The change was dependent on antigen cross-presenting CD8(+) dendritic cells, secretion of IFNγ, and CD4(+)T cells expressing CD40L. Antitumor CD8(+) T cells entered tumors shortly after radiotherapy, reversed MDSC infiltration, and mediated durable remissions in an IFNγ-dependent manner. Interestingly, extended fractionated radiation regimen did not result in robust CD8(+) T-cell infiltration.
For immunologically sensitive tumors, these results indicate that remissions induced by a short course of high-dose radiotherapy depend on the development of antitumor immunity that is reflected by the nature and kinetics of changes induced in the tumor cell microenvironment. These results suggest that systematic examination of the tumor immune microenvironment may help in optimizing the radiation regimen used to treat tumors by adding a robust immune response.
The results of investigations of mechanoactivation of a mixture of hafnium and carbon black powders in conditions of intensive vibration treatment using grinding bodies made of VK6 hard alloy and ...ShKh15 steel are presented. It is shown that the vibration treatment of the initial components leads to a mechanochemical synthesis of hafnium carbide starting from the first seconds of activation. Moreover, in the proposed treatment conditions, it is preferable to use steel grinding bodies.
Changes in the frequencies of cell subsets that (co)express characteristic biomarkers, or levels of the biomarkers on the subsets, are widely used as indices of drug response, disease prognosis, stem ...cell reconstitution, etc. However, although the currently available computational "gating" tools accurately reveal subset frequencies and marker expression levels, they fail to enable statistically reliable judgements as to whether these frequencies and expression levels differ significantly between/among subject groups. Here we introduce flow cytometry data analysis pipeline which includes the Earth Mover's Distance (EMD) metric as solution to this problem. Well known as an informative quantitative measure of differences between distributions, we present three exemplary studies showing that EMD 1) reveals clinically-relevant shifts in two markers on blood basophils responding to an offending allergen; 2) shows that ablative tumor radiation induces significant changes in the murine colon cancer tumor microenvironment; and, 3) ranks immunological differences in mouse peritoneal cavity cells harvested from three genetically distinct mouse strains.
Stages of multilayer carbon nanotube formation are studied during mechanical activation of amorphous carbon prepared by pyrolysis from plant raw material. It is shown that prolonged mechanical ...activation of a carbon composite in a vario-planetary mill (>36 h) leads to formation of aggregates and loss of nanotube thermal stability.
Mechanochemical synthesis of titanium carbide via vibrational activation was limited by the carbon structural modifications resulting from pyrolysis of plant biomass and the ash content of natural ...graphite. Natural graphite and amorphous carbon modifications prepared from plant biomass were demonstrated to be promising for synthesizing titanium carbide with minimal sulfur contents.
Rejection of ectopic heart transplants expressing OVA requires OVA-specific CD4 and CD8 T cells. In the absence of CD4 T cells, OVA-specific CD8 T cells proliferate and migrate to the graft, but fail ...to develop cytolytic functions. With CD4 T cells present, clonal expansion of the CD8 T cells is only marginally increased but the cells now develop effector functions and mediate rapid graft rejection. In the presence of CD4 T cells, Ag and B7 levels do not increase on dendritic cells but IL-12 production is up-regulated, and this requires CD154 expression on the CD4 T cells. OVA-specific CD8 T cells lacking the IL-12 receptor fail to differentiate or mediate graft rejection even when CD4 T cells are present. Thus, CD4 T cells condition dendritic cells by inducing the production of IL-12, which is needed as the "third signal" for CD8 T cell differentiation and avoidance of tolerance.
A complex of magnetic and magnetoacoustic properties of cold-deformed and annealed (at different temperatures) steels with carbon contents of 0.2 (20 steel) and 0.7% (70 steel) was investigated. It ...was established that as the annealing temperature of these steels increases up to 700°C, the values of the parameters that are related to the intensity of irreversible magnetization-reversal processes monotonically increase. It is shown that the coercive force of 70 steel changes nonmonotonically under variations in the annealing conditions and cannot be a testing parameter. Among quasi-statically measured magnetic parameters for testing the annealing procedure, the residual induction and the coercivereturn induction can be used. The structural sensitivities of such parameters of the magnetoacoustic emission (MAE) as the amplitude, the fundamental frequency, and the field of the MAE maximum were investigated. It is shown that the MAE maximum amplitude and field correlate with the residual magnetic induction of the substance of the investigated steels and can be used in the diagnostics.
T cells are widely used to promote engraftment of hematopoietic stem cells (HSCs) during an allogeneic hematopoietic cell transplantation. Their role in overcoming barriers to HSC engraftment is ...thought to be particularly critical when patients receive reduced doses of preparative chemotherapy and/or radiation compared with standard transplantations. In this study, we sought to delineate the effects CD4
cells on engraftment and blood formation in a model that simulates clinical hematopoietic cell transplantation by transplanting MHC-matched, minor histocompatibility-mismatched grafts composed of purified HSCs, HSCs plus bulk T cells, or HSCs plus T cell subsets into mice conditioned with low-dose irradiation. Grafts containing conventional CD4
T cells caused marrow inflammation and inhibited HSC engraftment and blood formation. Posttransplantation, the marrows of HSCs plus CD4
cell recipients contained IL-12-secreting CD11c
cells and IFN-γ-expressing donor Th1 cells. In this setting, host HSCs arrested at the short-term stem cell stage and remained in the marrow in a quiescent cell cycling state (G
). As a consequence, donor HSCs failed to engraft and hematopoiesis was suppressed. Our data show that Th1 cells included in a hematopoietic allograft can negatively impact HSC activity, blood reconstitution, and engraftment of donor HSCs. This potential negative effect of donor T cells is not considered in clinical transplantation in which bulk T cells are transplanted. Our findings shed new light on the effects of CD4
T cells on HSC biology and are applicable to other pathogenic states in which immune activation in the bone marrow occurs such as aplastic anemia and certain infectious conditions.
PDF
