Toll-like receptors in cancer

O’Neill, Luke A.J.

doi:10.1038/sj.onc.1210903

Cited by 14 publications

(23 citation statements)

References 8 publications

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“…The involvement of TLRs in the carcinogenesis of cancer cells has been reviewed extensively [29,[49][50][51]. Recently, TLR-related research has greatly advanced and shows promising therapeutic potential against diseases such as inflammation and cancer.…”

Section: Functional Relationships Between Antigen Receptors and Toll-mentioning

confidence: 99%

“…Furthermore, treatment of OC-3-VGH ovarian cancer cells and C-33A cervical cancer cells with RP215 or anti-antigen receptor antibodies resulted in upregulation of NFκB, which is also activated by the TLR signalling cascade [28]. NFκB is known to be a significant transcription factor involved in the gene regulations/expression of both antigen receptors and TLRs, as well as more than 200 other genes in a variety of biological functions in different cell types [29,[49][50][51][68][69][70][71]. Currently, the exact mechanism by which cancerous immunoglobulins alter TLR gene expression and cause upregulation of NFκB in cancer cells remains to be elucidated.…”

Section: Possible Roles Of Cancerous Immunoglobulins and Toll-like Rementioning

confidence: 99%

“…It was generally agreed that in cancer cells, TLRs play not only roles in microbial infection, inflammation, and tissue repair, but also in driving tumorigenesis upon stimulation [29,[49][50][51]. Based on these experimental observations, it can be concluded that these TLRs and cancerous immunoglobulins may play similar roles in neutralizing undesirable "antigens/ pathogens" in the innate immune system of cancer cells [28,29,[49][50][51]. Although the "antigens" recognized by cancerous immunoglobulins have yet to be defined and identified, the targeting ligands of these TLRs are known and well established [29].…”

Section: Functional Relationships Between Antigen Receptors and Toll-mentioning

confidence: 99%

“…Therefore, the effects of anti-antigen receptor antibodies and RP215 on the gene regulations of TLRs, which are essential elements of the innate immune system in cancer cells, were examined. TLRs are known to belong to the family of pattern-recognition receptors (PPRs) which recognize microbe-associated molecular patterns (MAMPs), and play important roles in innate immunity [29,[48][49][50][51]. In addition, TLRs are also involved in carcinogenesis and in the growth/proliferation of cancer cells [52][53][54][55][56][57][58][59].…”

Section: Effects Of Rp215 Anti-human Immunoglobulin G and Anti-t Cementioning

confidence: 99%

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Roles of antigen receptors and CA215 in the innate immunity of cancer cells

Lee¹,

Liu²

2013

OJI

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Antigen receptors, including immunoglobulins and T-cell receptors, are known to be widely expressed by cancer cells through unconfirmed mechanisms and for unknown purposes. Recently, a monoclonal antibody, designated as RP215, was generated against the ovarian cancer cell line, OC-3-VGH, and was shown to react with CA215, which consisted mainly of these cancer cell-expressed antigen receptors. Experimental evidence has clearly indicated that cancerous immunoglobulins play significant roles in the growth and proliferation of cancer cells in vitro and in vivo. RP215 and anti-antigen receptor antibodies were equally effective in inducing apoptosis and complement-dependent cytotoxicity reactions to cultured cancer cells. Through gene regulation studies, both RP215 and antibodies against antigen-receptors were shown to affect more than a dozen of genes involved in cell proliferation (such as NFκB-1, IgG, P21, cyclin D1, ribosomal P 1 , and c-fos). Furthermore, selected toll-like receptor genes (TLR-2, -3, -4, and -9) were also found to be highly regulated by both RP215 and anti-antigen receptor antibodies. For example, RP215 and antiantigen receptor antibodies were found to both up-regulate TLR-2 and/or TLR-3 and downregulate TLR-4 and TLR-9 in two types of cancer cells. Based on these studies, it is reasonable to postulate that cancerous immunoglobulins play important roles in the modulation of the innate immune system to allow the growth and survival of cancer cells within the human body. Consequently, RP215 in its humanized forms may be utilized to target cancer cells for potential therapeutic purposes.

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Section: Functional Relationships Between Antigen Receptors and Toll-mentioning

confidence: 99%

Section: Possible Roles Of Cancerous Immunoglobulins and Toll-like Rementioning

confidence: 99%

Section: Functional Relationships Between Antigen Receptors and Toll-mentioning

confidence: 99%

Section: Effects Of Rp215 Anti-human Immunoglobulin G and Anti-t Cementioning

confidence: 99%

See 2 more Smart Citations

Roles of antigen receptors and CA215 in the innate immunity of cancer cells

Lee¹,

Liu²

2013

OJI

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show abstract

“…These differences are detected by the numerous pattern receptors, which are a hallmark of the innate immune system. These pattern receptors include the Toll-like receptors, the subject of a recent Oncogene review issue (O'Neill, 2008). The activation of innate immunity leads to the efficient priming of adaptive immune responses mediated by B and T cells.…”

mentioning

confidence: 99%