ABSTRACT
Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal-associated invariant T (MAIT) cells play an important role in early anti-TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non-MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti-TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4-CD8- cells, and very few were CD4+ cells. After BCG infecting autologous antigen-presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1-specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti-TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti-TB immunotherapy.
ABSTRACT
The immune system provides full protection for the body by specifically identifying 'self' and removing 'others'; thus protecting the body from diseases. The immune system includes innate immunity and adaptive immunity, which jointly coordinate the antitumor immune response. T cells, natural killer (NK) cells and tumor-associated macrophages (TAMs) are the main tumor-killing immune cells active in three antitumor immune cycle. Cancer immunotherapy focusses on activating and strengthening immune response or eliminating suppression from tumor cells in each step of the cancer-immunity cycle; thus, it strengthens the body's immunity against tumors. In this review, the antitumor immune cycles of T cells, natural killer (NK) cells and tumor-associated macrophages (TAMs) are discussed. Co-stimulatory and co-inhibitory molecules in the three activity cycles and the development of drugs and delivery systems targeting these molecules are emphasized, and the current state of the art of drug delivery systems for cancer immunotherapy are summarized.
Subject(s)
Neoplasms , T-Lymphocytes , Humans , Tumor-Associated Macrophages/pathology , Killer Cells, Natural , Immunotherapy , Drug Delivery SystemsABSTRACT
INTRODUCTION: Reconstruction of the medial patellofemoral ligament (MPFL) is an effective surgical method for the treatment of lateral patellar instability. At present, there is not much controversies regarding the femoral attachment, however, the controversies regarding patellar attachment versus attachment, number of graft strands, tension, isometry and so on. The following electronic databases will be searched: PubMed, the Cochrane Library, Embase, Web of Science, Medline. We will consider articles published between database initiation and March 2021. MPFL in the subject heading will be included in the study. Language is limited to English. Research selection, data extraction, and research quality assessment were independently completed by 2 researchers. CONCLUSIONS: MPFL reconstruction is a reliable technique for the treatment of patellofemoral instability. The Schöttle point is still the mainstream method for locating the femoral attachment, the patellar attachment for single-bundle is located at the junction of the proximal one third and the distal two third of the longitudinal axis of the patella. For double-bundles, one is located in the proximal one third of the medial patellar edge and another is in the center of the patellar edge. Meanwhile, the adjustment of graft tension during operation is very important.
