ABSTRACT
IL-33 is a danger signal that binds to its receptor ST2L to promote tumor progression. This study identifies the IL-33/ST2L positive-feedback loop and the trafficking of ST2L membrane presentation in macrophages that contribute to lung tumor progression. Mechanistically, IL-33 induces ST2L upregulation by activating NF-κB, which binds to the promoter region of the ST2L gene. Moreover, Rab37, a small GTPase involved in membrane trafficking, mediates ST2L trafficking to the plasma membrane of M2 macrophages. This IL-33/NF-κB/ST2L/Rab37 axis promotes positive-feedback loops that enhance ST2L expression and membrane trafficking in M2 macrophages. Notably, neutralizing antibodies against IL-33 or ST2L block NF-κB activity, suppress M2 macrophage polarization, and synergistically inhibit tumor growth when combined with cisplatin treatment in vitro/vivo. Clinically, Rab37+/ST2L+/CD206+ tumor-infiltrating M2 macrophages correlate with advanced-stage lung cancer patients with poor response to chemotherapy. These findings unveil a positive-feedback mechanism and provide a basis for IL-33/ST2L-targeting therapy for cancer.
Subject(s)
Interleukin-33 , Lung Neoplasms , Macrophages , NF-kappa B , rab GTP-Binding Proteins , Interleukin-33/metabolism , Interleukin-33/genetics , Humans , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/genetics , NF-kappa B/metabolism , Macrophages/metabolism , Macrophages/drug effects , Animals , rab GTP-Binding Proteins/metabolism , rab GTP-Binding Proteins/genetics , Mice , Feedback, Physiological , Cell Line, Tumor , Signal Transduction/drug effects , Mice, Inbred C57BL , FemaleABSTRACT
We present a new ternary semiconductor absorber material - Pb1-xSnxS - for solar cells. Pb1-xSnxS nanocrystals (NCs) were synthesized using the successive ionic layer adsorption reaction (SILAR) process. Energy-dispersive X-ray spectroscopy revealed the Sn ratio for a sample prepared with five SILAR cycles to be x=0.55 (i.e. non-stoichiometric formula Pb0.45Sn0.55S). The optical spectra revealed that the energy gap Eg of the Pb1-xSnxS NCs decreased with an increasing number of SILAR cycles n, with Eg=1.67eV for the sample with n=5. Liquid-junction Pb1-xSnxS quantum dot-sensitized solar cells were fabricated using the polysulfide electrolyte. The best cell yielded a short-circuit current density Jsc of 10.1mA/cm2, an open circuit voltage of 0.43V, a fill factor FF of 50% and an efficiency of 2.17% under 1 sun. The external quantum efficiency spectrum (EQE) covered a spectral range of 300-800nm with a maximum EQE of â¼67% at λ=650nm. At the reduced light of 0.1 sun, the efficiency increased to 3.31% (with a normalized Jsc=17.7mA/cm2) - a respectable efficiency for a new sensitizer. This work demonstrates that Pb1-xSnxS shows potential as a solar cell absorber.
