Imiquimod Treatment of Superficial and Nodular Basal Cell Carcinoma: 12-Week Open-Label Trial

Peris, Ketty; Campione, Elena; Micantonio, Tamara; Marulli, Georgiana Clare; Fargnoli, Maria Concetta; Chimenti, Sergio

doi:10.1111/j.1524-4725.2005.31081

Cited by 58 publications

(53 citation statements)

References 39 publications

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“…The TLR7 agonist imiquimod is indeed already used as standard care for the topical treatment of some primary skin tumors. 8,18 We and others have shown that the systemic use of TLR7 agonists also blocks tumor growth in mice, an effect that is at least in part due to the enhancement of the antitumoral function of CD8 C T cells and NK cells as well as to the inhibition of Treg function. 10,19 Indeed, repeated treatment of CT26 tumor-bearing mice with the TLR7 ligand R848 inhibits tumor progression (Fig.…”

Section: Discussionmentioning

confidence: 99%

TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function

et al. 2016

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Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with the capacity to inhibit immunological responses. During cancer progression, MDSC are recruited to the tumor sites and secondary lymphoid organs, leading to the suppression of the antitumor function of NK and T cells. Here, we show that the TLR7/8 agonist resiquimod (R848) has a direct effect on MDSC populations in tumor-bearing mice. Systemic application of R848 led to a rapid reduction in both intratumoral and circulating MDSC. The subpopulation of monocytic MDSC (m-MDSC) was the most affected by R848 treatment with an up to 5-fold decrease in the tumor. We found that TLR7 stimulation in tumor-bearing mice led to a maturation and differentiation of MDSC with upregulation of the surface molecules CD11c, F4/80, MHC-I, and MHC-II. MDSC treated with R848 lost their immunosuppressive function and acquired instead an antigen-presenting phenotype with the capability to induce specific Tcell proliferation. Importantly, we found that MDSC co-injected s.c. with CT26 tumor cells lost their ability to support tumor growth after pretreatment with R848. Our results demonstrate that treatment of tumorbearing mice with a TLR7/8 agonist acts directly on MDSC to induce their maturation and leads them to acquire a non-suppressive status. Considering the obstacles posed by MDSC for cancer immunotherapy, targeting these cells by a TLR7/8 agonist may improve immune responses against cancer.

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Section: Discussionmentioning

confidence: 99%

TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function

et al. 2016

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“…4 Indeed, synthetic agonists for the RNA-sensing TLR7 are now an approved treatment for certain skin cancers and in clinical development for other malignancies. [5][6][7] Ligands targeting the RLR, RIG-I, and MDA-5 are also currently under development for cancer immunotherapy. 4,8,9 To transmit intracellular signaling, RLR and TLR employ different adaptor molecules; RLR utilize MAVS, 10 whereas TLR are coupled to MyD88 with the exception of TLR3, which exclusively signals via the adaptor TRIF.…”

Section: Introductionmentioning

confidence: 99%

Reprogramming of TLR7 signaling enhances antitumor NK and cytotoxic T cell responses

et al. 2016

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Toll-like receptor (TLR) 7 agonists are effective in topical application for the immunotherapy of skin cancers, but their performance for the systemic treatment of solid tumors is limited by the development of TLR tolerance. In this study, we describe a novel strategy to overcome TLR tolerance and enhance TLR7-dependent antitumor immune responses through reprogramming of TLR signaling pathways. The sensitivity of TLR7 signaling in dendritic cells (DC) was increased by prior stimulation with the dsRNA poly (I:C) that mimics virally induced immune activation. Timing of the stimulations was important, as sequential stimulation with poly(I:C) and the TLR7 agonist R848 interspaced by 24 h induced higher MAPK and NFkB signaling in DC than the simultaneous application of the same ligands. DC activated by sequential poly(I:C)/R848 stimulation efficiently induced Th1 differentiation and primed NK-cell and cytotoxic T-cell responses. We have developed a treatment regimen taking advantage of TLR7 reprogramming that cured over 80% of large immunogenic tumors in mice by the action of NK cells and cytotoxic T cells. These results have direct implications for the use of these clinically established ligands in the immunotherapy of cancer.

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“…Local relapse was observed in 2.9% of the patients during the observation period lasting up to 34 months (23 months on average). Local reaction was observed in 67.3% of the patients [9]. Lymphadenopathy was not diagnosed in any of the patients.…”

Section: Discussionmentioning

confidence: 88%

“…However, the data reflecting the frequency of relapse are not so optimistic and it reaches from 2.9% to as much as 16% in a period of observation exceeding 2 years [9,11]. There results from this an image of high frequency local relapse when imiquimod is applied in monotherapy, especially in comparison with surgical treatment, where the frequency of local relapse is 3-8% of patients.…”

Section: Discussionmentioning

confidence: 94%

Imiquimod as an alternative to surgery in the treatment of skin cancers – experience with the first group of patients

Murawa¹,

Połom²,

Murawa³

2011

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Imiquimod Treatment of Superficial and Nodular Basal Cell Carcinoma: 12-Week Open-Label Trial

Abstract: In our patient population, treatment of superficial BCCs with topical imiquimod for 12 weeks produced an excellent clinical response overall, with complete remission maintained after a mean of 23 months.

Cited by 58 publications

References 39 publications

TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function

TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function

Reprogramming of TLR7 signaling enhances antitumor NK and cytotoxic T cell responses

Imiquimod as an alternative to surgery in the treatment of skin cancers – experience with the first group of patients

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