Chimeric antigen receptor (CAR) T-cell therapies have been demonstrated to have durable and potentially curative therapeutic efficacies in patients with hematological malignancies. Currently, multiple clinical trials in CAR-T cell therapy have been evaluated for the treatment of patients with solid malignancies, but have had less marked therapeutic effects when the agents are used as monotherapies. When summarizing relevant studies, the present study found that combination therapy strategies for solid tumors based on CAR-T cell therapies might be more effective. This review will focus on various aspects of treating solid tumors with CAR-T cell therapy: i) The therapeutic efficacy of CAR-T cell monotherapy, ii) the feasibility of the CAR-T cell therapy in conjunction with chemotherapy, iii) the feasibility of CAR-T cell therapy with radiotherapy, iv) the feasibility of CAR-T cell therapy with chemoradiotherapy, and v) the feasibility of the combination of CAR-T cell therapy with other strategies.

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Background/Aims: The primary objective of this study was to investigate the role of miR-146a in inducing the inflammatory infiltration of macrophages in polymyositis/dermatomyositis (PM/DM) through targeting TNF receptor associated factor 6 (TRAF6), which may further down-regulate the Interleukin-17 (IL-17)/Intercellular Adhesion Molecule 1 (ICAM-1) pathway. Methods: Biopsies were collected from PM/DM patients and healthy volunteers. PM/DM model establishment and macrophage isolation were performed on Sprague Dawley (SD) rats. Model rats and macrophages were treated with anti-IL-17, anti-ICAM-1, miR-146a mimics, miR-146a inhibitors, and TRAF6 siRNAs. Serum creatine phosphokinase (S-CK) expression was assessed using double antibody sandwich enzyme-linked immunosorbent assay (ELISA) assay, and immunohistochemistry assay was performed to analyze CD163 expression in muscle samples. Furthermore, we used transwell assay to test cell migration; RT-PCR and western blot were carried out to determine the expression of miR-146a, TRAF6, IL-17, and ICAM-1. Results: The S-CK, TRAF6, IL-17 and ICAM-1 levels were higher in PM/DM patients compared with healthy controls and were down-regulated after the conventional treatment. Treatment with miR-146a mimics, anti-IL-17 and anti-ICAM-1 decreased the expression of IL-17 and ICAM-1, whereas miR-146a inhibitors exerted the opposite effects. The effects of miR-146a inhibitors were suppressed by treatment with TRAF6 siRNA. In addition, the luciferase reporter assay validated the targeting relationship between miR-146a and TRAF6. Conclusions: MiR-146a regulates inflammatory macrophage infiltration in PM/DM by targeting TRAF6 and affecting the IL-17/ICAM-1 pathway.

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Arsenic trioxide (ATO)-induced hepatotoxicity limits the therapeutic effect of acute myelogenous leukemia treatment. Magnesium isoglycyrrhizinate (MgIG) is a natural compound extracted from licorice and a hepatoprotective drug used in liver injury. It exhibits anti-oxidant, anti-inflammatory and anti-apoptotic properties. The aim of the present study was to identify the protective action and underlying mechanism of MgIG against ATO-induced hepatotoxicity. A total of 50 mice were randomly divided into five groups (n=10/group): Control; ATO; MgIG and high-and low-dose MgIG + ATO. Following continuous administration of ATO for 7 days, the relative weight of the liver, liver enzyme, histological data, antioxidant enzymes, pro-inflammatory cytokines, cell apoptosis and changes in Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) signaling pathway were observed. MgIG decreased liver injury, decreased the liver weight and liver index, inhibited oxidative stress and decreased the activity of glutathione, superoxide dismutase and catalase, production of reactive oxygen species and levels of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Western blotting showed a decrease in Bax and caspase-3. There was decreased cleaved caspase-3 expression and increased Bcl-2 expression. MgIG notably activated ATO-mediated expression of Keap1 and Nrf2 in liver tissue. MgIG administration was an effective treatment to protect the liver from ATO-induced toxicity. MgIG maintained the level of Nrf2 in the liver and protected the antioxidative defense system to attenuate oxidative stress and prevent ATO-induced liver injury.