Therapeutic targeting of immune checkpoints with small molecule inhibitors.

Abstract:

:Immune checkpoints are known to contribute to tumor progression by enhancing cancer's ability to evade the immune system and metastasize. Immunotherapies, including monoclonal antibodies, have been developed to target specific immunosuppressive molecules on the membranes of cancer cells and have proven revolutionary in the field of oncology. Recently, small molecule inhibitors (SMIs) have gained increased attention in cancer research with potential applications in immunotherapy. SMIs have desirable benefits over large-molecule inhibitors, such as monoclonal antibodies, including greater cell permeability, organ specificity, longer half-lives, cheaper production costs, and the possibility for oral administration. This paper will review the mechanisms by which noteworthy and novel immune checkpoints contribute to tumor progression, and how they may be targeted by SMIs and epigenetic modifiers to offer possible adjuvants to established therapeutic regimens. SMIs target immune checkpoints in several ways, such as blocking signaling between tumorigenic factors, building immune tolerance, and direct inhibition via epigenetic repression of immune inhibitory molecules. Further investigation into combination therapies utilizing SMIs and conventional cancer therapies will uncover new treatment options that may provide better patient outcomes across a range of cancers.

journal_name

Am J Transl Res

authors

Smith WM,Purvis IJ,Bomstad CN,Labak CM,Velpula KK,Tsung AJ,Regan JN,Venkataraman S,Vibhakar R,Asuthkar S

subject

Has Abstract

pub_date

2019-02-15 00:00:00

pages

529-541

issue

2

issn

1943-8141

journal_volume

11

pub_type

杂志文章,评审
  • Exercise training and immune crosstalk in breast cancer microenvironment: exploring the paradigms of exercise-induced immune modulation and exercise-induced myokines.

    abstract::Observational research suggests that exercise may reduce the risk of breast cancer and improve survival. One proposed mechanism for the protective effect of aerobic exercise related to cancer risk and outcomes, but has not been examined definitively, is the immune response to aerobic exercise. Two prevailing paradigms...

    journal_title:American journal of translational research

    pub_type: 杂志文章,评审

    doi:

    authors: Goh J,Niksirat N,Campbell KL

    更新日期:2014-10-11 00:00:00

  • All-trans-retinoic acid activates SDF-1/CXCR4/ROCK2 signaling pathway to inhibit chondrogenesis.

    abstract::Recent studies have indicated that ATRA inhibits chondrogenesis and can lead to congenital clubfoot (CCF). The molecular mechanism of ATRA-induced chondrogenesis is not clear. As RhoA/ROCK and SDF-1/CXCR4 signaling play important molecular roles for a variety of cellular processes, we hypothesized that RhoA/ROCK2 and ...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Hu QX,Li XD,Xie P,Wu CC,Zheng GZ,Lin FX,Xie D,Zhang QH,Liu DZ,Wang YG,Chang B,Du SX

    更新日期:2017-05-15 00:00:00

  • Ring finger protein 152 inhibits colorectal cancer cell growth and is a novel prognostic biomarker.

    abstract::Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. RING finger-related E3 ubiquitin ligases play a role in tumorigenesis and can function either as oncogenes or tumor suppressors based on their target proteins. Here, we show that the expression of RNF152, a ring finger protein, in CRC ti...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Cui X,Shen W,Wang G,Huang Z,Wen D,Yang Y,Liu Y,Cui L

    更新日期:2018-11-15 00:00:00

  • Hyperbaric oxygen treatment attenuates neuropathic pain by elevating autophagy flux via inhibiting mTOR pathway.

    abstract::Peripheral neuropathic pain is a complex disease, and treated based on underlying diseases. Emerging evidences suggest that hyperbaric oxygen alleviates neuropathic pain. However, its cellular and molecular mechanism on pain relief is unknown. We hypothesize that hyperbaric oxygen alleviates neuropathic pain via activ...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Liu YD,Wang ZB,Han G,Zhao P

    更新日期:2017-05-15 00:00:00

  • CircAPLP2 regulates the proliferation and metastasis of colorectal cancer by targeting miR-101-3p to activate the Notch signalling pathway.

    abstract::Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, and it has a poor prognosis. Emerging evidence shows that circular RNAs (circRNAs) may act as good therapeutic targets for cancers due to their abundance and stability. However, their regulatory role in CRC needs further investigation. This study r...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Wu HB,Huang SS,Lu CG,Tian SD,Chen M

    更新日期:2020-06-15 00:00:00

  • Probiotics enhance the effect of allergy immunotherapy on regulating antigen specific B cell activity in asthma patients.

    abstract::Immune regulatory system dysfunction plays a role in the pathogenesis of asthma. The therapeutic effect of allergic asthma is to be improved. The immune regulatory function of probiotics has been recognized. This study tests a hypothesis that Clostridium butyricum (CB) enhances the effect of allergen specific immunoth...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Liu J,Chen FH,Qiu SQ,Yang LT,Zhang HP,Liu JQ,Geng XR,Yang G,Liu ZQ,Li J,Liu ZG,Li HB,Yang PC

    更新日期:2016-12-15 00:00:00

  • Identification of three glioblastoma subtypes and a six-gene prognostic risk index based on the expression of growth factors and cytokines.

    abstract::Glioblastoma multiforme (GBM) is the most common and invasive tumor of the central nervous system. Growth factors and cytokines (GFCKs) play a crucial role in tumor invasion. In the present study, GFCK expression profiles from GBM patients in the Chinese Glioma Genome Atlas were used to perform sample clustering with ...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Hu B,Ruan Y,Wei F,Qin G,Mo X,Wang X,Zou D

    更新日期:2020-08-15 00:00:00

  • MicroRNA-29 family inhibits rhabdomyosarcoma formation and progression by regulating GEFT function.

    abstract::The microRNA-29 family, which contains mir-29a, mir-29b, and mir-29c, can promote or resist the development of several types of tumors. However, its role in rhabdomyosarcoma (RMS) has not been determined. In this work, we detected the expression of mir-29a/b/c in RMS. Results showed that the tissues and cell lines in ...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Wang Y,Zhang L,Pang Y,Song L,Shang H,Li Z,Liu Q,Zhang Y,Wang X,Li Q,Zhang Q,Liu C,Li F

    更新日期:2020-03-15 00:00:00

  • The chemokine receptor CCR1 is identified in mast cell-derived exosomes.

    abstract::Mast cells are important effector cells of the immune system, and mast cell-derived exosomes carrying RNAs play a role in immune regulation. However, the molecular function of mast cell-derived exosomes is currently unknown, and here, we identify differentially expressed genes (DEGs) in mast cells and exosomes. We iso...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Liang Y,Qiao L,Peng X,Cui Z,Yin Y,Liao H,Jiang M,Li L

    更新日期:2018-02-15 00:00:00

  • Preliminary study of urine metabolism in type two diabetic patients based on GC-MS.

    abstract:OBJECTIVE:Comparative study of type 2 diabetes and healthy controls by metabolomics methods to explore the pathogenesis of Type II diabetes. METHODS:Gas chromatography - mass spectrometry (GC-MS) with a variety of multivariate statistical analysis methods to the healthy control group 58 cases, 68 cases of Type II diab...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Zhang N,Geng F,Hu ZH,Liu B,Wang YQ,Liu JC,Qi YH,Li LJ

    更新日期:2016-07-15 00:00:00

  • Therapeutic effects of adipose derived fresh stromal vascular fraction-containing stem cells versus cultured adipose derived mesenchymal stem cells on rescuing heart function in rat after acute myocardial infarction.

    abstract::We tested the hypothesis that adipose-derived fresh stromal vascular fraction (SVF) is non-inferior to conventional adipose-derived mesenchymal stem cell (ADMSC) therapy for improving left-ventricular ejection fraction (LVEF) in rat after acute myocardial infarction (AMI). Male-adult SD rats (n = 48) were categorized ...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Sheu JJ,Lee MS,Wallace CG,Chen KH,Sung PH,Chua S,Lee FY,Chung SY,Chen YL,Li YC,Yip HK

    更新日期:2019-01-15 00:00:00

  • The mechanism of acetylcholine receptor in binding MuSK in myasthenia gravis and the role of HSP90 molecular chaperone.

    abstract::As an autoimmune disease, myasthenia gravis is caused by the dysfunction of neural transmission. Acetylcholine is known to exert its function after entering into synaptic cleft through binding onto postsynaptic membrane. The role of acetylcholine in binding MuSK in myasthenia gravis, however, remains unknown. A total ...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Chen R,Chen S,Liao J,Chen X,Xu X

    更新日期:2016-04-15 00:00:00

  • Reduction of depression symptoms in laryngeal cancer patients receiving psychology services.

    abstract::Depression is prevalence in patients with laryngeal cancer. In this study, we aim to investigate whether psychological intervention could reduce the depression of patients receiving cancer treatment. In this study, 258 patients with laryngeal cancer were assigned into two groups with or without psychological intervent...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Zhang S,Chen H,Zhang M,Sun X,Liu X

    更新日期:2020-10-15 00:00:00

  • MicroRNA-130a-3p suppresses cell viability, proliferation and invasion in nasopharyngeal carcinoma by inhibiting CXCL12.

    abstract::Incidence of nasopharyngeal carcinoma (NPC) has remained high worldwide, posing a serious health problem. MicroRNAs (miRNAs) are a family of about 20-23 nucleotides small non-coding molecules, which play a significant role in NPC. In this study, we explored the molecular mechanisms of miR-130a-3p in inhibiting viabili...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Qu R,Sun Y,Li Y,Hu C,Shi G,Tang Y,Guo D

    更新日期:2017-08-15 00:00:00

  • Long noncoding RNA MALAT1 and its target microRNA-125b are potential biomarkers for Alzheimer's disease management via interactions with FOXQ1, PTGS2 and CDK5.

    abstract::This study aimed to investigate the intercorrelation among long noncoding RNA MALAT1 (lnc-MALAT1), microRNA-125b (miR-125b), FOXQ1, PTGS2 and CDK5, as well as their correlations with disease risk, severity and progression of Alzheimer's disease (AD). In total, 120 AD patients, 120 Parkinson's disease (PD) patients and...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Zhuang J,Cai P,Chen Z,Yang Q,Chen X,Wang X,Zhuang X

    更新日期:2020-09-15 00:00:00

  • The effects of miRNA-1180 on suppression of pancreatic cancer.

    abstract::The aim of this study was to evaluate the effects of miR-1180 on pancreatic cancer. We sampled adjacent cancer and carcinoma tissues from 30 pancreatic cancer patients and measured miR-1180 expression by qRT-PCR and NF-κB protein expression by immunohistochemistry. To explore the effects of this miRNA in cell culture,...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Gu L,Zhang J,Shi M,Peng C

    更新日期:2017-06-15 00:00:00

  • Peptide nucleic acids targeting mitochondria enhances sensitivity of lung cancer cells to chemotherapy.

    abstract::Acquired resistance to chemotherapy is a major limitation for the successful treatment of lung cancer. Previously, we and others showed that formation of tumor spheres is associated with chemotherapy resistance in lung cancer cells, but the underlying mechanisms remained largely unknown. In the current study, we show ...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Chen SS,Tu XY,Xie LX,Xiong LP,Song J,Ye XQ

    更新日期:2018-09-15 00:00:00

  • Physiological regulation of Akt activity and stability.

    abstract::The serine/threonine protein kinase B (PKB, also known as Akt) constitutes an important node in diverse signaling cascades downstream of growth factor receptor tyrosine kinases. Akt plays an essential role in cell survival, growth, migration, proliferation, polarity, and metabolism (lipid and glucose); cell cycle prog...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Liao Y,Hung MC

    更新日期:2010-01-01 00:00:00

  • Herbal Formula-3 ameliorates OVA-induced food allergy in mice may via modulating the gut microbiota.

    abstract::Formula-3 is a Chinese herbal medicine formula that was shown to inhibit food allergy in rats by stabilizing mast cells. But whether Formula-3 ameliorates food allergy through modulating the composition of intestinal microbiota remains to be explored. Here, we aimed to determine whether gut microbiota mediate the anti...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Liu S,Yang B,Yang P,Liu Z

    更新日期:2019-09-15 00:00:00

  • Erythema elevatum diutinum involving palms and soles: a case report and literature review.

    abstract::Erythema elevatum diutinum (EED) is a rare chronic inflammatory dermatosis and a part of the spectrum of cutaneous leukocytoclasticvasculitis. The most common site of involvement is extensor surface of the extremities, with a predilection for the skin overlying joints, particularly hands, feet, elbows and knees, as we...

    journal_title:American journal of translational research

    pub_type:

    doi:

    authors: Keyal U,Bhatta AK,Liu Y

    更新日期:2017-04-15 00:00:00

  • Diverse involvement of EZH2 in cancer epigenetics.

    abstract::EZH2 is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2) which catalyzes methylation of histone H3 at lysine 27 (H3K27me) and mediates gene silencing of target genes via local chromatin reorganization. Numerous evidences show that EZH2 plays a critical role in cancer initiation, progression and metastasis,...

    journal_title:American journal of translational research

    pub_type: 杂志文章,评审

    doi:

    authors: Völkel P,Dupret B,Le Bourhis X,Angrand PO

    更新日期:2015-02-15 00:00:00

  • The effects of adipose-derived mesenchymal stem cells combined with sodium selenite on Hashimoto's thyroiditis.

    abstract::Recent research found that sodium selenite (Na2SeO3) could ameliorate oxidative damage in patients with Hashimoto's thyroiditis (HT). Additionally, the effects of adipose-derived mesenchymal stem cells (AMSCs) in an animal model of HT were also reported. However, the effects of AMSCs combined with Na2SeO3 on HT are un...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Che K,Liu X,Chi J,Li P,Gao J,Fu Z,Yan S,Xing X,Hu J

    更新日期:2020-10-15 00:00:00

  • ROC-supervised principal component analysis in connection with the diagnosis of diseases.

    abstract::Principal component analysis (PCA) is a data analysis method that can deal with large volumes of data. Owing to the complexity and volume of the data generated by today's advanced technologies in genomics, pro-teomics, and metabolomics, PCA has become predominant in the medical sciences. Despite its popularity, PCA le...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Nikas JB,Low WC

    更新日期:2011-02-01 00:00:00

  • Genetic myostatin decrease in the golden retriever muscular dystrophy model does not significantly affect the ubiquitin proteasome system despite enhancing the severity of disease.

    abstract::Recent studies suggest that inhibiting the protein myostatin, a negative regulator of skeletal muscle mass, may improve outcomes in patients with Duchenne muscular dystrophy by enhancing muscle mass. When the dystrophin-deficient golden retriever muscular dystrophy (GRMD) dog was bred with whippets having a heterozygo...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Cotten SW,Kornegay JN,Bogan DJ,Wadosky KM,Patterson C,Willis MS

    更新日期:2013-12-01 00:00:00

  • Epirubicin pretreatment enhances NK cell-mediated cytotoxicity against breast cancer cells in vitro.

    abstract::Anthracycline-based chemotherapy is a conventional treatment for breast cancer. However, it can negatively affect host immune function and thereby impair patients' quality of life. Boosting the host immune system and reducing the adverse effect of chemotherapy are important for effective cancer treatment. Natural kill...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Feng H,Dong Y,Wu J,Qiao Y,Zhu G,Jin H,Cui J,Li W,Liu YJ,Chen J,Song Y

    更新日期:2016-02-15 00:00:00

  • Liraglutide suppresses TNF-α-induced degradation of extracellular matrix in human chondrocytes: a therapeutic implication in osteoarthritis.

    abstract::Osteoarthritis (OA) is a major global health problem; however, the etiology of the disease remains unknown and a reliable treatment strategy has yet to be discovered. Modulation of the receptor for glucagon-like peptide 1 (GLP-1) has emerged as a potential treatment strategy for various diseases including OA. In the p...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Mei J,Sun J,Wu J,Zheng X

    更新日期:2019-08-15 00:00:00

  • Modulation of NFAT-5, an outlying member of the NFAT family, in human keratinocytes and skin.

    abstract:BACKGROUND:Cyclosporin A (CsA) and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). NFAT compose a family of transcription factors that are turned on during ...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Al-Daraji WI,Afolayan J,Zelger BG,Abdellaoui A,Zelger B

    更新日期:2009-01-22 00:00:00

  • A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3'- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer.

    abstract:UNLABELLED:3, 3'-diindolylmethane (DIM) modulates estrogen metabolism and acts as an anti-androgen which down-regulates the androgen receptor and prostate specific antigen (PSA). We conducted a dose-escalation, phase I study of BioResponse (BR)-DIM with objectives to determine the maximum tolerated dose (MTD), toxicity...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Heath EI,Heilbrun LK,Li J,Vaishampayan U,Harper F,Pemberton P,Sarkar FH

    更新日期:2010-07-23 00:00:00

  • Expression profile of ACTL8, CTCFL, OIP5 and XAGE3 in glioma and their prognostic significance: a retrospective clinical study.

    abstract:BACKGROUND:Cancer/testis antigens (CTAs) are attractive therapeutic targets for tumor immunotherapy due to their restrictive expression in normal testis but excessive in majority of tumor types. ACTL8, CTCFL, OIP5 and XAGE3 are members of the CTAs family. Currently, the data of ACTL8, CTCFL, OIP5 and XAGE3 expression i...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Li X,Ning L,Zhang Q,Ge Y,Liu C,Bi S,Zeng X,Nong W,Wu S,Guo G,Xiao S,Luo B,Xie X

    更新日期:2020-12-15 00:00:00

  • HOE-642 improves the protection of hypothermia on neuronal mitochondria after cardiac arrest in rats.

    abstract::HOE-642 has been shown to provide significant protection in a variety of models of cerebral and myocardial ischemia/reperfusion injury. In this study, we examined the impact of HOE-642, a selective Na+/H+ exchanger 1 inhibitor, with or without hypothermia on neuronal and neuronal mitochondrial function during resuscit...

    journal_title:American journal of translational research

    pub_type: 杂志文章

    doi:

    authors: Wei L,Zhang P,Hu Y,Zhao W,Liu X,Wang X,Han F

    更新日期:2020-05-15 00:00:00