Low Density In-Medium Effects on Light Clusters from Heavy-Ion Data.

The modification of the ground state properties of light atomic nuclei in the nuclear and stellar medium is addressed, using chemical equilibrium constants evaluated from a new analysis of the intermediate energy heavy-ion (Xe+Sn) collision data measured by the INDRA Collaboration. Three different reactions are considered, mainly differing by the isotopic content of the emission source. The thermodynamic conditions of the data samples are extracted from the measured multiplicities allowing for a parametrization of the in-medium modification, determined with the single hypothesis that the different nuclear species in a given sample correspond to a unique common value for the density of the expanding source. We show that this correction, which was not considered in previous analyses of chemical constants from heavy-ion collisions, is necessary, since the observables of the analyzed systems show strong deviations from the expected results for an ideal gas of free clusters. This dataset is further compared to a relativistic mean-field model, and seen to be reasonably compatible with a universal correction of the attractive σ-meson coupling.

Defective Interferon Gamma Production by Tumor-Specific CD8+ T Cells Is Associated With 5'Methylcytosine-Guanine Hypermethylation of Interferon Gamma Promoter.

Interferon gamma (IFNγ) supports effector responses of CD8+ cytotoxic T lymphocytes (CTLs) and is a surrogate marker for detection of antigen-specific T cells. Here, we show that tumor-specific CTL clones have impaired IFNγ expression and production upon activation. Assessment of the relationship between IFNγ production and the 5'methylcytosine-guanine (CpG) dinucleotide methylation of the IFNγ promoter using bisulfite treatment has shown that IFNγ- CTL clones accumulates CpG hypermethylation within the promoter at key transcription factor binding sites (-186 and -54), known to be vital for transcription. We confirmed these findings using ex vivo isolated and short-term expanded bulk tumor-specific CTL lines from four cancer patients and demonstrated that IFNγ methylation inversely correlates with transcription, protein level, and cytotoxicity. Altogether, we propose that a sizeable portion of human tumor-specific CTLs are deficient in IFNγ response, contributed by CpG hypermethylation of the IFNγ promoter. Our findings have important implications for immunotherapy strategies and for methods to detect human antigen-specific T cells.