ABSTRACT
Myeloid-derived suppressor cells (MDSCs) are recognized as major immune suppressor cells in the tumor microenvironment that may inhibit immune checkpoint blockade (ICB) therapy. Here, we developed a Stattic-loaded mesoporous silica nanoparticle (PEG-MSN-Stattic) delivery system to tumor sites to reduce the number of MDSCs in tumors. This approach is able to significantly deplete intratumoral MSDCs and thereby increase the infiltration of T lymphocytes in tumors to enhance ICB therapy. Our approach may provide a drug delivery strategy for regulating the tumor microenvironment and enhancing cancer immunotherapy efficacy.
Subject(s)
Immunotherapy , Myeloid-Derived Suppressor Cells , Nanoparticles , Silicon Dioxide , Tumor Microenvironment , Silicon Dioxide/chemistry , Nanoparticles/chemistry , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/drug effects , Immunotherapy/methods , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Animals , Mice , Porosity , Humans , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/drug therapy , Cell Line, Tumor , Drug Carriers/chemistry , Drug Delivery Systems , Polyethylene Glycols/chemistryABSTRACT
Severe pneumonia may induce sequelae and accelerated aging process even after the person has recovered. However, the underline mechanism is not very clear. More research is needed to fully understand the long-term effects of severe pneumonia. In this study, we found that mice recovered from severe pneumonia showed lung immunosenescence, which was characterized by a bias naive-memory balance of T lymphocytes in the lung. The reduction of naïve T cells is associated with the diminished immune response to cancer or external new antigens, which is one of the key changes that occurs with age. Our results also indicate the link between severe pneumonia and aging process, which is mediated by the disrupted T cells homeostasis in the lungs after pneumonia.
