Frontiers in immunology
-
Frontiers in immunology · Jan 2018
ReviewEngineering CAR-T Cells for Improved Function Against Solid Tumors.
Genetic engineering T cells to create clinically applied chimeric antigen receptor (CAR) T cells has led to improved patient outcomes for some forms of hematopoietic malignancies. While this has inspired the biomedical community to develop similar strategies to treat solid tumor patients, challenges such as the immunosuppressive character of the tumor microenvironment, CAR-T cell persistence and trafficking to the tumor seem to limit CAR-T cell efficacy in solid cancers. This review provides an overview of mechanisms that tumors exploit to evade eradication by CAR-T cells as well as emerging approaches that incorporate genetic engineering technologies to improve CAR-T cell activity against solid tumors.
-
Frontiers in immunology · Jan 2018
Clinical TrialFunctional, Antigen-Specific Stem Cell Memory (TSCM) CD4+ T Cells Are Induced by Human Mycobacterium tuberculosis Infection.
Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM) or effector (TEFF) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM. We aimed to determine if infection with Mycobacterium tuberculosis (M. tb), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology. ⋯ Human infection with M. tb induced distinct, antigen-specific CD4+ TSCM cells endowed with effector functions, including expression of cytotoxic molecules and Th1 cytokines, and displayed chemokine receptor profiles consistent with memory Th1/17 cells. Induction of CD4+ TSCM should be considered for vaccination approaches that aim to generate long-lived memory T cells against M. tb.
-
Frontiers in immunology · Jan 2018
Low-Dose Mycophenolate Mofetil for Treatment of Neuromyelitis Optica Spectrum Disorders: A Prospective Multicenter Study in South China.
Objective: To evaluate the efficacy and safety of low-dose mycophenolate mofetil (MMF, 1,000 mg/day) treatment of neuromyelitis optica spectrum disorders (NMOSDs). Methods: This study was a multicenter, open, prospective, follow-up clinical trial. The data include retrospective clinical data from the pretreatment phase and prospective data from the post-treatment phase. ⋯ Fourteen (16%) of the total patients discontinued MMF after our last follow-up for various reasons and switched to azathioprine or rituximab. Conclusion: Low-dose MMF reduced clinical relapse and disability in NMOSD patients in South China. However, some patients still suffered from adverse events at this dosage.
-
Frontiers in immunology · Jan 2018
Granulocytic Myeloid-Derived Suppressor Cells (GR-MDSC) in Breast Milk (BM); GR-MDSC Accumulate in Human BM and Modulate T-Cell and Monocyte Function.
Nosocomial bacterial infections (NBI) and necrotizing enterocolitis (NEC) are among the main reasons for death in preterm infants. Both are often caused by bacteria coming from the infected infant's gut and feeding with breast milk (BM) seems beneficial in their pathogenesis. However, mechanisms causing the protective effect of BM are only incompletely understood. ⋯ Furthermore, we found that the lactotrophic hormones prolactin and oxytocin do not induce MDSC from peripheral blood. This is the first study to describe MDSC with immune-modulatory properties in human BM. Our results point toward a role for MDSC in local immune modulation in the gut possibly protecting infants from NBI and NEC.
-
Frontiers in immunology · Jan 2018
Glibenclamide Reduces Primary Human Monocyte Functions Against Tuberculosis Infection by Enhancing M2 Polarization.
Tuberculosis (TB) is a global public health problem, which is caused by Mycobacterium tuberculosis (Mtb). Type 2 diabetes mellitus (T2DM) is one of the leading predisposing factors for development of TB after HIV/AIDS. Glibenclamide is a widely used anti-diabetic drug in low and middle-income countries where the incidence of TB is very high. ⋯ In contrast, M2 (CD163+ and CD206+) surface markers and IL-10 production were enhanced by pretreatment with glibenclamide. Additionally, reduction of bactericidal activity also occurred when primary human monocytes from T2DM individuals who were being treated with glibenclamide were infected with Mtb in vitro, consistent with the cytokine responses. We conclude that glibenclamide reduces M1 and promotes M2 polarization leading to impaired bactericidal ability of primary human monocytes of T2DM individuals in response to Mtb and may lead to increased susceptibility of T2DM individuals to TB and other bacterial infectious diseases.