Cancer relapse under chemotherapy: Why TLR2/4 receptor agonists can help

Garay, Ricardo P.; Viens, Patrice; Bauer, Jacques; Normier, G.; Bardou, Marc; Jeannin, Jean–François; Chiavaroli, Carlo

doi:10.1016/j.ejphar.2007.02.018

Cited by 109 publications

(101 citation statements)

References 120 publications

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“…Previous studies suggested that HMGB1 is one of the key modulators of tumor development and its receptor, the receptor for advanced glycation end products (RAGE) [55] or Toll Like Receptor4 (TLR4) [35], is expressed on variety of cancer cells [66][67][68][69] including colon cancer [69]. HMGB1 was reported to have a potential role in the regulation of cancer autophagy and apoptosis as response to the administration of anti-cancer agent [42] as well as to regulate migration and sprouting of endothelial cells as angiogenesis in tumor progression [35].…”

Section: Discussionmentioning

confidence: 99%

Human Mesenchymal Stem Cells Migrate toward Colon Cancer Partially Regulated by HMGB1

Yagi¹

2013

J Cell Sci Ther

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Although Mesenchymal Stem Cells (MSC) has been explored as a new clinically relevant cell type to repair injured tissue, a number of studies have highlighted the important aspect of MSC therapy. Studies have shown that systemically administered MSCs migrate to sites of malignant tumor. The focus of this study was to identify the mechanism of migration of human MSCs into cancerous tissue. First, the effect of cultured medium from cancer cell lines on modulating the migration of MSCs was evaluated, using seven different human colon cancer cell lines. Interestingly, the secretion level of High Mobility Group Box 1 (HMGB1) protein from each cell line affected the migration capacity of MSCs. In addition, recombinant human HMGB1 increased MSC's migration capacity in a dosedependent manner. Finally, 1×10 6 human MSCs were injected subcutaneously into mice (n=14) with colon cancer tumors that secreted high levels of HMGB1. Bioluminescence live image analysis showed that MSCs surrounded the tumors after injection into these mice through day 6. Immunohistochemical analysis using CD90 as a specific antibody revealed the existence of MSCs in and around the tumors as well as the secretion of local HMGB1 from the tumors detected by anti-HMGB1 antibody. These findings are critical in understanding the role of MSCs in development of solid tumors and further, they offer insight that may be useful in therapeutic application of MSCs in the treatment of malignant tumors.

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Section: Discussionmentioning

confidence: 99%

Human Mesenchymal Stem Cells Migrate toward Colon Cancer Partially Regulated by HMGB1

Yagi¹

2013

J Cell Sci Ther

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“…During the past couple of decades, dozens of immunity-related molecules including PRRs have been identified, and their identifications greatly help us to understand the relationship between innate immunity and cancer. Among the above mentioned classical BRMs, the following TLRs have been shown to mediate their anti-tumor effects; TLR4 for Coley toxin (Garay et al, 2007) and OK-432 (Hironaka et al, 2006;Okamoto et al, 2006), TLR2/TLR4 for BCG-CWS (Uehori et al, 2005), respectively. TLR agonists mediate anti-tumor activity by multiple mechanisms (Rakoff-Nahoum & Medzhitov, 2008).…”

Section: Anti-tumor Effects Induced By Tlr Signalingmentioning

confidence: 99%

“…Breaking the tolerance to tumor self-antigens is a property known as adjuvanticity. The mechanisms by which TLRs induce effective antitumor adaptive immune responses include the uptake, processing and presentation of tumor antigens, enhancement of survival, and induction of costimulatory molecules on professional APCs, induction of Th1 and CTL responses, and the inhibition of regulatory T cell activity (Garay et al, 2007;Smyth et al, 2006;Akazawa et al, 2007).…”

Section: Anti-tumor Effects Induced By Tlr Signalingmentioning

confidence: 99%

“…TLR agonists have been shown to directly kill both tumor cells and ancillary cells of the tumor microenvironment, such as vascular endothelium (Salaun et al, 2006;El Andaloussi et al, 2006;Haimovitz-Friedman et al, 1997;Nogueras et al, 2008). TLR activation may also lead to tumor regression directly or indirectly (TNF-mediated) by increasing vascular permeability (Garay et al, 2007), recruitment of leukocytes, activation of the tumor lytic activity of NK cells and cytotoxic T lymphocytes (CTL), and increasing the sensitivity of tumor cells to elimination mechanisms by effector molecules, such as TRAIL, TNF, and granzyme B/perforin (Smyth et al, 2006;Akazawa, 2007).…”

Section: Anti-tumor Effects Induced By Tlr Signalingmentioning

confidence: 99%

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Innate Immunity-Based Immunotherapy of Cancer

Maruyama¹,

Ishii²,

Tai³

et al. 2012

Advancements in Tumor Immunotherapy and Cancer Vaccines

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“…Garay 144 reviewed the potential benefits of TLR agonists when added to chemotherapy TLR2/4 agonists to induce well-controlled TNFα secretion at plasma levels known to make neoangiogenic tumour vessels permeable to the passage of cytotoxic drugs. Moreover, TLR2/4 agonists induce expression of inducible nitric oxide synthase, and nitric oxide is able to induce apoptosis of chemotherapy-resistant tumour cell clones.…”

Section: Herbsmentioning

confidence: 99%

Chinese Medicine and Biomodulation in Cancer Patients—Part Two

Sagar

Wong

2008

Current Oncology

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Traditional Chinese Medicine (TCM) is a whole system containing therapeutic interventions that individually induce biomodulation at the physiologic, chemical, and molecular levels. The theory of TCM proposes a synergy between specific interventions selected as part of a care plan based on TCM diagnostic theory. Combining TCM with the modern practice of oncology seems, in conjunction with biomedical interventions (surgery, radiotherapy, chemotherapy, and pharmaceuticals), to have potential advantages through the synergy of biomodulation. Biomodulation approaches are broadly categorized as modification of tumour response and reduction of adverse effects; modulation of immunity; prevention of cancer progression; and enhancement of symptom control. Although the database of preclinical studies is rapidly expanding, good-quality clinical trials are notably scarce.Laboratory studies suggest that some herbs increase the effectiveness of conventional chemotherapy without increasing toxicity. A healthy immune system is necessary for control of malignant disease, and the immune suppression associated with cancer contributes to its progression. Many Chinese herbs contain glycoproteins and polysaccharides (among them, constituents of Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, Astragalus membranaceus, Panax ginseng, and various other medicinal mushrooms) that can modulate metastatic potential and the innate immune system. Phytochemicals such as specific polysaccharides have been shown to boost the innate immune system, especially through interaction with Tolllike receptors in mucosa-associated lymphoid tissue. This intervention can potentially improve the effectiveness of new anticancer vaccines. An increase in virusassociated cancers presents a major public health problem that requires novel therapeutic strategies. A number of herbal therapies have both antiviral activity and the ability to promote immunity, possibly inhibiting the initiation and promotion of virus-associated cancers.The mechanisms learned from basic science should be applied to clinical trials both of specific interventions and of whole-system care plans that safely combine the TCM approach with the conventional biomedical model. In Western medicine, the combination of TCM herbs with drug therapies is controversial, given lack of knowledge concerning whether a drug is favourably enhanced or whether adverse effects occur. Using initial data from the preclinical studies, future clinical research needs to evaluate the combinations, some of which are showing favourable synergy.

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Cancer relapse under chemotherapy: Why TLR2/4 receptor agonists can help

Cited by 109 publications

References 120 publications

Human Mesenchymal Stem Cells Migrate toward Colon Cancer Partially Regulated by HMGB1

Human Mesenchymal Stem Cells Migrate toward Colon Cancer Partially Regulated by HMGB1

Innate Immunity-Based Immunotherapy of Cancer

Chinese Medicine and Biomodulation in Cancer Patients—Part Two

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