Chimeric Antigen Receptor T (CAR-T) cell therapy represents a groundbreaking advancement in cancer treatment, demonstrating remarkable antitumor efficacy in hematological malignancies. However, despite the substantial clinical progress achieved with CAR-T cell therapy, its application in the treatment of solid tumors remains limited by various factors, including the intricate tumor microenvironment (TME), CAR-T cell exhaustion, CAR-T cell infiltration into tumor tissue, and antigen heterogeneity. Scientists are relentlessly pursuing research in this domain, driven by the aim of offering newfound hope to cancer patients. In this comprehensive review, we delineate the fundamental principles underlying CAR-T cell therapy, delve into the challenges it encounters, and provide an insightful exploration of the advancements and progress made in the application of CAR-T cell therapy for solid tumors.
Chronic inflammation is widely considered a risk factor for T2DM by inducing insulin resistance, but all attempts to translate the concept into clinical therapies have failed in the past 30 years. Anti-inflammatory medicines, including anti-TNF-α antibody (Etanercept), anti-IL1 antibody (Anakinra), anti-IL6 (Ziltivekimab), and NLRP3 inflammasome inhibitor (Colchicine) have excellent activities in the control of inflammation in arthritis. They reduced inflammation in T2DM patients in the clinical trials, but none improved insulin sensitivity. Some of them exhibited a mild and transient activity in the control of blood glucose, but the activities were related to the improvement of insulin secretion by β-cells. The failure may be related to followings: over-interpretation of TNF-α activity; ignoring the role of anti-inflammatory cytokines; differences between mice and humans. However, the species difference cannot fully explain the failure as these therapies did not work in the animal models as well. Moreover, genome-wide association studies (GWAS) show that T2DM is not associated with proinflammatory cytokine genes, including TNF-α, IL-1β, IL-6, and CCL2(MCP1). More studies suggest that inflammation has beneficial activities in the mobilization of energy stores and promotion of energy expenditure to prevent energy surplus, a risk factor of obesity-associated T2DM. Inflammatory cytokines induce lipolysis, thermogenesis, and satiety. In this regard, the inflammatory response is a compensatory event to obesity-associated stress with beneficial effects on energy metabolism. It is time to reconsider inflammation activity in obesity for protective activities.
Autoimmune encephalitis has reshaped the understanding of neuropsychiatric disorders by highlighting the role of autoantibodies in psychosis symptoms, which often mimic primary psychosis conditions. This review synthesizes recent research on autoimmune encephalitis-related psychosis, broadening the focus from humoral immunity to T cell autoimmunity and the communication between the peripheral and central nervous systems. We discuss the identification of neuronal antigen targets, particularly the N-methyl-D-aspartate receptor (NMDAR), and their involvement in disease pathogenesis. Current treatments, such as plasma exchange and intravenous immunoglobulin, primarily target the pathogenicity of autoantibodies. However, emerging evidence suggests a crucial role for T cells, glia cell, and B cell in the immunopathogenesis of autoimmune encephalitis-related psychosis diseases. Autoimmune factors, including T and B cells, can either infiltrate the brain from the periphery or propagate via interacting with other cells, like glia, within the brain itself. This review advocates for a comprehensive approach to studying and treating these conditions, integrating both humoral and cellular mechanisms.
