Microbial hydrogen "manufactory" for enhanced gas therapy and self-activated immunotherapy via reduced immune escape.

BACKGROUND: As an antioxidant, hydrogen (H2) can selectively react with the highly toxic hydroxyl radical (·OH) in tumor cells to break the balance of reactive oxygen species (ROS) and cause oxidative stress. However, due to the high diffusibility and storage difficulty of hydrogen, it is impossible to achieve long-term release at the tumor site, which highly limited their therapeutic effect. RESULTS: Photosynthetic bacteria (PSB) release a large amount of hydrogen to break the balance of oxidative stress. In addition, as a nontoxic bacterium, PSB could stimulate the immune response and increase the infiltration of CD4+ and CD8+ T cells. More interestingly, we found that hydrogen therapy induced by our live PSB did not lead to the up-regulation of PD-L1 after stimulating the immune response, which could avoid the tumor immune escape. CONCLUSION: Hydrogen-immunotherapy significantly kills tumor cells. We believe that our live microbial hydrogen production system provides a new strategy for cancer hydrogen treatment combining with enhanced immunotherapy without up-regulating PD-L1.

Therapeutic exosomal vaccine for enhanced cancer immunotherapy by mediating tumor microenvironment.

Tumor immunotherapy has been convincingly demonstrated as a feasible approach for treating cancers. Although promising, the immunosuppressive tumor microenvironment (TME) has been recognized as a major obstacle in tumor immunotherapy. It is highly desirable to release an immunosuppressive "brake" for improving cancer immunotherapy. Among tumor-infiltrated immune cells, tumor-associated macrophages (TAMs) play an important role in the growth, invasion, and metastasis of tumors. The polarization of TAMs (M2) into the M1 type can alleviate the immunosuppression of the TME and enhance the effect of immunotherapy. Inspired by this, we constructed a therapeutic exosomal vaccine from antigen-stimulated M1-type macrophages (M1OVA-Exos). M1OVA-Exos are capable of polarizing TAMs into M1 type through downregulation of the Wnt signaling pathway. Mediating the TME further activates the immune response and inhibits tumor growth and metastasis via the exosomal vaccine. Our study provides a new strategy for the polarization of TAMs, which augments cancer vaccine therapy efficacy.

A CAR T-inspiring platform based on antibody-engineered exosomes from antigen-feeding dendritic cells for precise solid tumor therapy.

Chimeric antigen receptor T (CAR T) cell therapy has achieved remarkable results treating patients with hematological malignancies in clinical studies. Although promising, extensive research has also revealed that CAR T therapy is unsatisfactory for the treatment of solid tumors. In addition, the production of CAR T cells is time-consuming and it's hard for storage and transportation. In this work, inspired by the construction of CAR T cell, we developed an antibody-engineered exosomes from antigen-feeding dendritic cells for beyond CAR T therapy of solid tumor by in situ T cells activation and cancer cell targeting. We have confirmed that tumor antigen-stimulated dendritic cell-derived exosomes (tDC-Exo) provided major histocompatibility (MHC)-antigen complexes and CD86 co-stimulating molecules, which were the same as CAR of CAR T cell acting as the necessary signals for T cell activation. Furthermore, anti-CD3 and anti-EGFR were then engineered on tDC-Exo to promote the binding of T cell to cancer cells for precise therapy. Our CAR T cell therapy-mimicking system have shown an efficient endogenous T cells activation and their crosslinking with cancer cells for enhanced solid tumor therapy. More interestingly, we found that immune activation significantly up-regulated PD-L1 expression, and thus we confirmed the combination with anti-PD-L1 antibodies further enhanced the efficacy of our CAR T cell therapy-mimicking platform.

[Spatial-temporal variations of extractable organic matter in atmospheric PM10 and PM2.5 in Beijing].

PM10 and PM2.5 samples were collected in parallel in different function zones of Beijing during four seasons of 2005. The pollution level, distribution characteristics of the extractable organic matter (EOM) and relationship between EOM (PM10) and EOM (PM2.5) were illustrated. The results show that: the annual mean concentrations of organic compound in PM10 and PM2.5 are 41.39 microg/m3 and 34.84 microg/m3, being 1.44 times and 1.26 times higher than Ming Tombs site. The concentrations of EOM in winter are 67.04 microg/m3 (PM10) and 64.64 microg/m3 (PM2.5), which are 1.15 and 1.82 times, 2.06 and 2.26 times, 4.53 and 6.26 times higher than that in spring, autumn, summer, respectively. Ratios of EOM in PM2.5 to that in PM10 in different seasons exceed 0.60. In different function zones the concentrations of EOM present industrial and commercial zones > living, traffic and contrast zones. The influence of EOM (PM2.5) on EOM (PM10) in different districts are various. The order of annual concentrations of organic compositions is non-hydrocarbons > asphaltenes > aromatics > saturated hydrocarbon. The seasonal emissions of pollution sources play an important role in seasonality of compositions of EOM.