Targeting Toll-like receptors against cancer

Du, Bing; Jiang, Qiuli; Cleveland, Joseph C.; Liu, Bing-Rong; Zhang, Dekai

doi:10.20517/2394-4722.2016.62

Cited by 23 publications

(18 citation statements)

References 71 publications

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“…They have also been associated with the pathogenesis of several human cancers including B cell malignancies, colorectal cancer, basal cell carcinoma, bladder cancer, including several other cancers [485][486][487][488][489]. This involvement of TLRs in the pathogenesis of autoimmune diseases and cancers has led to the development novel immunotherapies for these diseases [490][491][492][493][494]. Even TLR mediated immune stimulation approach is now being used to enhance radiation therapy to control tumor growth [495].…”

Section: Future Perspectivementioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

529

346

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The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.

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Section: Future Perspectivementioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

529

346

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“…Combining a blockade of inhibitory signals with the delivery of activating signals should improve the efficacy of immunotherapies. Many possible approaches of this type are being tested, including the triggering of innate immunity via the delivery of TLR ligands ( Du et al., 2016 ), activation of the STING pathway at the tumor bed ( Corrales et al., 2016 ), treatment with antibodies targeting activating cell surface receptors ( Callahan et al., 2016 , Muntasell et al., 2017 ), and the use of engineered forms of cytokines, such pegylated IL-2 ( Charych et al., 2017 , Charych et al., 2016 ) and IL-2 variants ( Sockolosky et al., 2018 ). Antibodies directed against tumor cells also could be used to stimulate the immune response to tumor cells, thereby helping to eliminate cancer.…”

Section: Discussionmentioning

confidence: 99%

Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells

Pèlegrin¹,

Denis²,

Soulas³

et al. 2018

Cell

925

894

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SummaryCheckpoint inhibitors have revolutionized cancer treatment. However, only a minority of patients respond to these immunotherapies. Here, we report that blocking the inhibitory NKG2A receptor enhances tumor immunity by promoting both natural killer (NK) and CD8+ T cell effector functions in mice and humans. Monalizumab, a humanized anti-NKG2A antibody, enhanced NK cell activity against various tumor cells and rescued CD8+ T cell function in combination with PD-x axis blockade. Monalizumab also stimulated NK cell activity against antibody-coated target cells. Interim results of a phase II trial of monalizumab plus cetuximab in previously treated squamous cell carcinoma of the head and neck showed a 31% objective response rate. Most common adverse events were fatigue (17%), pyrexia (13%), and headache (10%). NKG2A targeting with monalizumab is thus a novel checkpoint inhibitory mechanism promoting anti-tumor immunity by enhancing the activity of both T and NK cells, which may complement first-generation immunotherapies against cancer.

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“…In addition, TLR may help the immune system to act as a defensive mechanism against the malignant transformation of the cells. Therefore, TLR agonists frequently have been used as immune adjuvants in anticancer immunotherapy (31,32).…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Expression of TLR-4 and Its Correlation to Various Grades of Oral Squamous Cell Carcinoma

Omar

El‐Sheikh

et al. 2018

Alexandria Dental Journal

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INTRODUCTION:Oral cancer is a major health problem, causing high morbidity and mortality rates. Oral squamous cell carcinoma (OSCC) accounts for 90-95% of all oral malignancies. During the last decade, significant evidence has suggested that inflammation plays an important role in tumorigenesis, and microenvironment-derived signals which are important constituents in all tumors. Toll-like receptors (TLRs) are classical signals that play a key role in the innate immune system. They drive the inflammatory response and control the cellular proliferation and survival by stimulating the immune cells and promoting integrated processes of inflammation and tissue repair. This can predict that TLR-4 may be of great significance in tumors. Hence, this study is to evaluate and correlate the expression of TLR-4 in various grades of oral squamous cell carcinoma (OSCC). OBJECTIVES: To evaluate and correlate the expression of TLR-4 in different histopathological grades of OSCC MATERIALS AND METHODS: An immunohistochemical (IHC) study using the TLR-4 antibody were done on 50 surgical specimens and 10 normal mucosal tissues taken from OSCC patients and healthy individuals, respectively. The staining were performed using a Labeled Strept-Avidin Biotin complex method (LSAB) RESULTS: TLR-4 was expressed in human OSCC biopsies and the expression level was correlated with the tumor differentiation. Higher expression was detected in the well and the moderately differentiated squamous cell carcinomas than the poorly differentiated ones. CONCLUSIONS: TLR-4 expression could be a prognostic factor in oral squamous cell carcinoma cases as expression was detected in the well and moderately differentiated higher than poorly differentiated squamous cell carcinomas.

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Targeting Toll-like receptors against cancer

Cited by 23 publications

References 71 publications

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells

Immunohistochemical Expression of TLR-4 and Its Correlation to Various Grades of Oral Squamous Cell Carcinoma

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