Advances in Immunosuppressive Agents Based on Signal Pathway

Xu, Zhiqing; Chu, Ming

doi:10.3389/fphar.2022.917162

Cited by 11 publications

(11 citation statements)

References 468 publications

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“…Deletion or downregulation of components of the JAK pathway can lead to tumor cells evading recognition by immune cells. On the other hand, the JAK signaling pathway also mediates cytokine regulation of immune cell proliferation, differentiation, and maturation (34). Overall, we uncovered more interesting findings that may guide selection criteria for ACC-targeted immunotherapy.…”

Section: Discussionmentioning

confidence: 78%

Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma

Liu

Liang

et al. 2022

Front. Endocrinol.

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Adrenocortical carcinoma (ACC) is a rare endocrine tumor, and most cases present with hormone excess with poor prognosis. Our research aims to determine the clinical and biological significance of glucocorticoid receptor (GR) expression using large cohorts of ACC patients. Immunohistochemistry was used to assess the expression of GR in 78 ACC cases from the West China Hospital (WCH) cohort. RNA-seq data were retrieved from The Cancer Genome Atlas database (TCGA, n=79). Clinicopathological and follow-up data were obtained from two cohorts. The correlation between the GR gene and tumor immune status was estimated using TIMER and GEPIA2. Kaplan–Meier analysis was performed to identify the prognostic value of GR in ACC. In the WCH cohort, positive nuclear GR staining was identified in 90% of the primary ACC cases. Cortisol-secreting ACCs demonstrated significantly lower GR protein expression than did nonfunctioning tumors (P<0.001). This finding was validated by the mRNA data analysis of the TCGA cohort (P = 0.030). GR expression was found to be positively correlated with the immune cell infiltration level and immune-checkpoint-related gene expression in ACC. Survival comparison and multivariate analysis showed that GR expression is an independent prognostic predictor of disease-free survival and overall survival in ACC patients in both cohorts. Our findings suggest that low GR expression is significantly correlated with excess cortisol, immune signatures and poor survival in ACC patients. We propose that GR signaling may play an important role in ACC behavior and thus may be a therapeutic target, which deserves further research.

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Section: Discussionmentioning

confidence: 78%

Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma

Liu

Liang

et al. 2022

Front. Endocrinol.

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Section: Pe Inhibited Nf-kb Activation and Promoted Activation Of Erk...mentioning

confidence: 99%

“…NF-kB, Akt, and MAPK signalling pathways are important for regulating inflammatory responses (31). Increased phosphorylation levels of p65 and Akt represent activation of NF-kB and Akt signaling pathways respectively (31). The MAPKs in mammals include p38, ERK and JNK which are serine-threonine protein kinases that regulate various cellular functions including inflammation (32).…”

Section: Pe Inhibited Nf-kb Activation and Promoted Activation Of Erk...mentioning

confidence: 99%

α1-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS

Cong

Yang²,

Zeng³

et al. 2023

Front. Immunol.

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IntroductionCatecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating adrenergic receptors (ARs). But the role of α1-AR in this process has yet to be elucidated.MethodsIn this study, ARDS mouse model was induced by intratracheal instillation of lipopolysaccharide. After treatment with α1-AR agonist phenylephrine or antagonist prazosin, lung pathological injury, alveolar barrier disruption and inflammation, and haemodynamic changes were evaluated. Cytokine levels and cell viability of alveolar macrophages were measured in vitro. Nuclear factor κB (NF-κB), mitogen-activated protein kinase, and Akt signalling pathways were analysed by western blot.ResultsIt showed that α1-AR activation alleviated lung injuries, including reduced histopathological damage, cytokine expression, and inflammatory cell infiltration, and improved alveolar capillary barrier integrity of ARDS mice without influencing cardiovascular haemodynamics. In vitro experiments suggested that α1-AR stimulation inhibited secretion of TNF-α, IL-6, CXCL2/MIP-2, and promoted IL-10 secretion, but did not affect cell viability. Moreover, α1-AR stimulation inhibited NF-κB and enhanced ERK1/2 activation without significantly influencing p38, JNK, or Akt activation.DiscussionOur studies reveal that α1-AR stimulation could ameliorate lipopolysaccharide-induced lung injury by inhibiting NF-κB and promoting ERK1/2 to suppress excessive inflammatory responses of alveolar macrophages.

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“…Also, as future perspectives, mTOR inhibitors should be considered immunosuppressive drugs that reduce or suppress the activity of the immune system [ 58 ]. They can be prescribed for the treatment of autoimmune diseases (systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease) or the prevention of graft rejection in organ transplants (liver, kidney, heart) [ 115 ]. The main advantage of immunosuppressive therapy is the improvement of the patient's quality of life [ 110 ].…”

Section: Therapeutic Perspectives Limitations and Challenges Associat...mentioning

confidence: 99%

Recent advances and limitations of mTOR inhibitors in the treatment of cancer

et al. 2022

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The PI3K-Akt-mechanistic (formerly mammalian) target of the rapamycin (mTOR) signaling pathway is important in a variety of biological activities, including cellular proliferation, survival, metabolism, autophagy, and immunity. Abnormal PI3K-Akt-mTOR signalling activation can promote transformation by creating a cellular environment conducive to it. Deregulation of such a system in terms of genetic mutations and amplification has been related to several human cancers. Consequently, mTOR has been recognized as a key target for the treatment of cancer, especially for treating cancers with elevated mTOR signaling due to genetic or metabolic disorders. In vitro and in vivo, rapamycin which is an immunosuppressant agent actively suppresses the activity of mTOR and reduces cancer cell growth. As a result, various sirolimus-derived compounds have now been established as therapies for cancer, and now these medications are being investigated in clinical studies. In this updated review, we discuss the usage of sirolimus-derived compounds and other drugs in several preclinical or clinical studies as well as explain some of the challenges involved in targeting mTOR for treating various human cancers.

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Advances in Immunosuppressive Agents Based on Signal Pathway

Cited by 11 publications

References 468 publications

Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma

Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma

α1-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS

Recent advances and limitations of mTOR inhibitors in the treatment of cancer

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