Topical Imiquimod: Mechanism of Action and Clinical Applications

Vidal, David

doi:10.2174/138955706776876131

Cited by 41 publications

(26 citation statements)

References 55 publications

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“…Bacillus Calmette-Guerin has not only been used as adjuvant but has also been administered alone to patients for postoperative treatments of cancer, producing good prognosis (33). Another example of antitumoral effect mediated by a TLR-agonist is the use of imiquimod, a small-molecule immune response modifier of the imidazoquinoline family that has shown profound antitumoral and antiviral efficacy both in vitro and in clinical applications in vivo (34). Imiquimod combines multiple, Figure 5.…”

Section: Discussionmentioning

confidence: 99%

Activation of Toll-like Receptor 4 on Tumor CellsIn vitroInhibits Subsequent Tumor GrowthIn vivo

et al. 2007

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Although an eruption of information on the role of Toll-like receptor 4 (TLR4), the main receptor for bacterial lipopolysaccharide, in activating macrophages and dendritic cells has emerged, very little is known about the role of TLR4 present on epithelial cells from sterile environments like tumors. The main goal of this work was to investigate the consequences of TLR4 activation present on tumor cells in two different animal models of cancer: the Dunning rat prostate cancer and the B16 murine melanoma models. We show that (a) activating TLR4 signaling in two different tumor cell lines in vitro modifies the tumor outgrowth in vivo; (b) this effect is not due to a direct consequence of TLR4 signaling on the proliferation/apoptosis balance of the tumor cells; (c) the T-cell compartment is somehow involved in the described phenomenon because the inhibitory effect observed is not seen in athymic nude mice; and (d) tumor-infiltrating lymphocytes purified from tumors induced by TLR4-activated cells show strong induction of IFN; transcript in detriment of interleukin-10 transcript, suggesting a change in their functionality. We hypothesize that TLR4 signaling in tumor cells in vitro induces the expression of proinflammatory mediators, which could dramatically alter the maturation state of dendritic cells present at the site of inoculation, switching the type of immune response elicited against the tumor. These results open up new avenues for understanding the role of TLR4 in tumor cells and for identifying potential new therapy strategies for cancer.

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Section: Discussionmentioning

confidence: 99%

Activation of Toll-like Receptor 4 on Tumor CellsIn vitroInhibits Subsequent Tumor GrowthIn vivo

et al. 2007

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“…A inibição da angiogênese é envolvida na atividade antitumoral e, nas malignidades cutâneas, ele rapidamente aumenta o infiltrado inflamatório peritumoral 1 . O IM é aprovado para o tratamento de verrugas genitais externas e perianais, queratoses actínicas e malignidades cutâneas, como carcinoma basocelular (CBC).…”

Section: Discussionunclassified

Remissão de lentigo maligno extenso após tratamento com imiquimod

Piazza

Sampaio

2009

An. Bras. Dermatol.

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Lentigo maligno é um melanoma in situ que mais comumente surge em áreas expostas à radiação ultravioleta, nos pacientes idosos. O tratamento é realizado, principalmente, para minimizar o risco de progressão para lentigo maligno melanoma. O presente relato se refere a uma paciente idosa com lesões recorrentes de lentigo maligno na face, tratada com sucesso com imiquimod tópico, mostrando que este pode ser um tratamento útil, em determinados casos da doença.

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“…59 Direct application of topical imiquimod has demonstrated clinical responses in various cutaneous metastases of the skin. 60,61 This antitumor activity is likely directed through TLR-dependent (TLR-7/TLR-8 activation of APCs) and independent (tumor apoptosis) pathways. 62 One immune-mediated mechanism of action for imiquimod is TLR-7 activation of plasmacytoid DCs (pDCs), leading to IFNα production that activates and matures myeloid-derived DCs (mDCs), leading to production of proinflammatory cytokines and enhanced antigen presentation that activates adaptive immunity (Table 3).…”

Section: Chemotherapymentioning

confidence: 99%

Enhancing immune responses to tumor-associated antigens

Higgins¹,

Bernstein²,

Hodge³

2009

Cancer Biology & Therapy

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The goal of vaccine-based cancer immunotherapy is to induce a tumor-specific immune response that ultimately reduces tumor burden. However, the immune system is often tolerant to antigens presented by the tumor, as the cancer originates from within a patient and is therefore recognized as self. This article reviews selected clinical strategies for overcoming this immune tolerance, and approaches to enhance generation of immunity to tumor-associated antigens by activating innate immunity, potentiating adaptive immunity, reducing immunosuppression, and enhancing tumor immunogenicity. Success in the field of cancer vaccines has yet to be fully realized, but intelligent choice of immunomodulators, tumor antigens and patient populations will likely lead to clinically relevant uses for cancer vaccines.

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Topical Imiquimod: Mechanism of Action and Clinical Applications

Cited by 41 publications

References 55 publications

Activation of Toll-like Receptor 4 on Tumor CellsIn vitroInhibits Subsequent Tumor GrowthIn vivo

Activation of Toll-like Receptor 4 on Tumor CellsIn vitroInhibits Subsequent Tumor GrowthIn vivo

Remissão de lentigo maligno extenso após tratamento com imiquimod

Enhancing immune responses to tumor-associated antigens

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