Toll-like receptor-induced cytokines as immunotherapeutic targets in cancers and autoimmune diseases

Patra, Mahesh Chandra; Shah, Masaud; Choi, Sangdun

doi:10.1016/j.semcancer.2019.05.002

Cited by 63 publications

(46 citation statements)

References 251 publications

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“…Aberrant activation of signaling pathways downstream of TLRs is also known to contribute to cancer progression and overproduction of proinflammatory cytokines underlying cachexia (110). Some studies demonstrated that the notorious TLR/myeloid differentiation factor 88 (TLR/MyD88) signaling (70) mediates skeletal muscle wasting during CC (71,111).…”

Section: Dysregulated Pathways In Smmentioning

confidence: 99%

Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options

2020

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Cancer cachexia (CC) is a multifactorial syndrome characterized by systemic inflammation, uncontrolled weight loss and dramatic metabolic alterations. This includes myofibrillar protein breakdown, increased lipolysis, insulin resistance, elevated energy expediture, and reduced food intake, hence impairing the patient's response to anti-cancer therapies and quality of life. While a decade ago the syndrome was considered incurable, over the most recent years much efforts have been put into the study of such disease, leading to the development of potential therapeutic strategies. Several important improvements have been reached in the management of CC from both the diagnostic-prognostic and the pharmacological viewpoint. However, given the heterogeneity of the disease, it is impossible to rely only on single variables to properly treat patients presenting this metabolic syndrome. Moreover, the cachexia symptoms are strictly dependent on the type of tumor, stage and the specific patient's response to cancer therapy. Thus, the attempt to translate experimentally effective therapies into the clinical practice results in a great challenge. For this reason, it is of crucial importance to further improve our understanding on the interplay of molecular mechanisms implicated in the onset and progression of CC, giving the opportunity to develop new effective, safe pharmacological treatments. In this review we outline the recent knowledge regarding cachexia mediators and pathways involved in skeletal muscle (SM) and adipose tissue (AT) loss, mainly from the experimental cachexia standpoint, then retracing the unimodal treatment options that have been developed to the present day.

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Section: Dysregulated Pathways In Smmentioning

confidence: 99%

Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options

2020

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“…In humans, this TLR is constitutively expressed in B cells and plasmacytoid dendritic cells (pDCs) and to some extent is also expressed in activated neutrophils, monocytes/macrophages, cDCs, and T-cells. In addition, TLR9 has been shown to be expressed in some non-immune cells, including keratinocytes and gut, cervical, and respiratory epithelial cells (37,62,63). FIGURE 1 | TLR9 signaling to produce inflammatory cytokines and type I IFNs.…”

Section: Tlr9 Function Cellular Localization and Signalingmentioning

confidence: 99%

“…TLRs are broadly expressed in immune cells for the detection of microbial pathogens to initiate host responses to infection (32)(33)(34). Synthetic TLR agonists such as imiquimod have been approved for anti-virus and cancer therapies, and others are being investigated for mono-or combination cancer therapies (10,(35)(36)(37). In the following discussion, we will focus on advances in the use of CpG-oligodeoxynucleotide (CpG-ODN), a synthetic TLR9 agonist to increase the efficacy of cancer immunotherapy with checkpoint blockade.…”

Section: Introductionmentioning

confidence: 99%

Adjuvant Effect of Toll-Like Receptor 9 Activation on Cancer Immunotherapy Using Checkpoint Blockade

et al. 2020

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Immunotherapy using checkpoint blockade has revolutionized cancer treatment, improving patient survival and quality of life. Nevertheless, the clinical outcomes of such immunotherapy are highly heterogeneous between patients. Depending on the cancer type, the patient response rates to this immunotherapy are limited to 20-30%. Based on the mechanism underlying the antitumor immune response, new therapeutic strategies have been designed with the aim of increasing the effectiveness and specificity of the antitumor immune response elicited by checkpoint blockade agents. The activation of toll-like receptor 9 (TLR9) by its synthetic agonists induces the antitumor response within the innate immunity arm, generating adjuvant effects and priming the adaptive immune response elicited by checkpoint blockade during the effector phase of tumor-cell killing. This review first describes the underlying mechanisms of action and current status of monotherapy using TLR9 agonists and immune checkpoint inhibitors for cancer immunotherapy. The rationale for combining these two agents is discussed, and evidence indicating the current status of such combination therapy as a novel cancer treatment strategy is presented.

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“…ADs are a set of chronic diseases that inadvertently activate the immune system against self-antigens and various organs of the body, leading to inflammation and tissue damage in patients [ 6 ]. Continuous production of cytokines leads to the loss of tolerance to self-antigens, which causes ADs and worsens the condition in ADs patients [ 7 , 8 ]. Due to the undeniable role of inflammatory cytokines in patients with ADs, COVID-19 can be cured through a treatment plan aiming to inhibit the over-activation of the immune system and control of cytokine production [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

The potential similarities of COVID-19 and autoimmune disease pathogenesis and therapeutic options: new insights approach

et al. 2020

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Cytokine pathways and their signaling disorders can be the cause of onset and pathogenesis of many diseases such as autoimmune diseases and COVID-19 infection. Autoimmune patients may be at higher risk of developing infection due to the impaired immune responses, the use of immunosuppressive drugs, and damage to various organs. Increased secretion of inflammatory cytokines and intolerance of the patient's immune system to COVID-19 infection are the leading causes of hospitalization of these patients. The content used in this paper has been taken from English language articles (2005-2020) retrieved from the PubMed database and Google Scholar search engine using "COVID-19," "Autoimmune disease," "Therapeutic," "Pathogenesis," and "Pathway" keywords. The emergence of COVID-19 and its association with autoimmune disorders is a major challenge in the management of these diseases. The results showed that the use of corticosteroids in the treatment of autoimmune diseases can make diagnosis and treatment of COVID-19 more challenging by preventing the fever. Due to the common pathogenesis of COVID-19 and autoimmune diseases, the use of autoimmune drugs as a possible treatment option could help control the virus. Key Points • Inflammatory cytokines play an essential role in the pathogenesis of COVID-19 • ACE2 dysfunctions are related to the with COVID-19 and autoimmune diseases • The use autoimmune diseases drugs can be useful in treating COVID-19

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Toll-like receptor-induced cytokines as immunotherapeutic targets in cancers and autoimmune diseases

Cited by 63 publications

References 251 publications

Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options

Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options

Adjuvant Effect of Toll-Like Receptor 9 Activation on Cancer Immunotherapy Using Checkpoint Blockade

The potential similarities of COVID-19 and autoimmune disease pathogenesis and therapeutic options: new insights approach

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