Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Dark Matter Search in Dwarf Irregular Galaxies with Ten Years of Data from the Ice Cube Neutrino Observatory

Dwarf irregular galaxies(dIrrs),as rotationally supported systems,have more reliable J-factor measurements than dwarf spheroidal galaxies and have received attention as targets for dark matter detection in recent years.In this paper,we use 10 yr of IceCube muon-track data and an unbinned maximum-likelihood-ratio method to search for neutrino signals beyond the background from the directions of seven dIrrs,aiming to detect neutrinos produced by heavy annihilation dark matter.We do not detect any significant signal.Based on such null results,we calculate the upper limits on the velocity-averaged annihilation cross section for 1 TeV–10 PeV dark matter.Our limits,although weaker than the strictest constraints in the literature in this mass range,are also a good complement to the existing results considering the more reliable J-factor measurements of dIrrs.

Search for gamma-ray line signals around the black hole at the galactic center with DAMPE observation

The adiabatic growth of a black hole(BH)may enhance the dark matter(DM)density surrounding it,causing a spike in the DM density profile.The spike around the supermassive BH at the center of the Milky Way may lead to a dramatic enhancement of the gamma-ray flux of DM annihilation from the galactic center(GC).In this work,we analyze the gamma-ray data of the innermost region(i.e.,the inner 1°)of the GC to search for potential line-like signals from the BH spike.Such line-like signals could be generated in the process of DM particles annihilating into double photons.We adopt the gamma-ray data from the Dark Matter Particle Explorer(DAMPE).Although the DAMPE has a much smaller effective area than the Fermi-LAT,the gamma-ray line search can benefit from its unprecedented high energy resolution.No significant line-like signals are found in our analysis.We derive upper limits on the cross section of the annihilation based on this non-detection.We find that despite the DAMPE’s small effective area for photon detection,we can still place strong constraints on the cross section(<σv>≥10^(-27)cm^(3)s^(-1))in the spike scenario due to the very bright model-expected flux from the spike.Our results indicate that either DM does not annihilate primarily through theγγchannel in the mass range we considered or no sharp density spike is present at the GC.