American Association for Cancer Research
10780432ccr120984-sup-ccr-12-0984fig1.pdf (69.09 kB)

Supplementary Figure 1 from Synergy of Topical Toll-like Receptor 7 Agonist with Radiation and Low-Dose Cyclophosphamide in a Mouse Model of Cutaneous Breast Cancer

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journal contribution
posted on 2023-03-31, 17:46 authored by M. Zahidunnabi Dewan, Claire Vanpouille-Box, Noriko Kawashima, Sara DiNapoli, James S. Babb, Silvia C. Formenti, Sylvia Adams, Sandra Demaria

PDF file - 69K, Supplementary Figure 1. Response of TSA cells to imiquimod in vitro. TSA cells were cultured in the presence of imiquimod or vehicle control at the indicated concentrations in triplicate wells. Data are expressed as percentage viable cells compared to control � SD. Errors bars are present but were very small. Data are representative of two independent experiments.



Purpose: This study tested the hypothesis that topical Toll-like receptor (TLR) 7 agonist imiquimod promotes antitumor immunity and synergizes with other treatments in a model of skin-involving breast cancer.Experimental Design: TSA mouse breast carcinoma cells were injected s.c. into syngeneic mice. Imiquimod 5% or placebo cream was applied topically on the shaved skin overlying tumors three times/wk. In some experiments, local ionizing radiation therapy (RT) was delivered to the tumor in three fractions of 8 Gy, given on consecutive days. Cyclophosphamide was given intraperitoneally (i.p.) in one dose of 2 mg/mouse. Mice were followed for tumor growth and survival.Results: Treatment with imiquimod significantly inhibited tumor growth, an effect that was associated with increased tumor infiltration by CD11c+, CD4+, and CD8+ cells, and abolished by depletion of CD8+ cells. Administration of imiquimod in combination with RT enhanced significantly tumor response compared with either treatment alone (P < 0.005), and 11% to 66% of irradiated tumors completely regressed. Importantly, the addition of topical imiquimod also resulted in growth inhibition of a secondary tumor outside of the radiation field. Low-dose cyclophosphamide given before start of treatment with imiquimod and RT further improved tumor inhibition and reduced tumor recurrence. Mice that remained tumor-free rejected a tumorigenic inoculum of TSA cells, showing long-term immunologic memory.Conclusions: Topical imiquimod inhibits tumor growth and synergizes with RT. Addition of cyclophosphamide further increases the therapeutic effect and induces protective immunologic memory, suggesting that this combination is a promising strategy for cutaneous breast cancer metastases. Clin Cancer Res; 18(24); 6668–78. ©2012 AACR.