Transcriptomic profiles conducive to immune-mediated tumor rejection in human breast cancer skin metastases treated with Imiquimod

Rozenblit, M., Hendrickx, W., Heguy, A., Chiriboga, L., Loomis, C., Ray, K., Darvishian, F., Egeblad, M., Demaria, S., Marincola, F. M., Bedognetti, D., Adams, S. (June 2019) Transcriptomic profiles conducive to immune-mediated tumor rejection in human breast cancer skin metastases treated with Imiquimod. Sci Rep, 9 (1). p. 8572. ISSN 2045-2322

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Abstract

Imiquimod is a topical toll-like-receptor-7 agonist currently used for treating basal cell carcinoma. Recently, imiquimod has demonstrated tumor regression in melanoma and breast cancer skin metastases. However, the molecular perturbations induced by imiquimod in breast cancer metastases have not been previously characterized. Here, we describe transcriptomic profiles associated with responsiveness to imiquimod in breast cancer skin metastases. Baseline and post-treatment tumor samples from patients treated with imiquimod in a clinical trial were profiled using Nanostring technology. Through an integrative analytic pipeline, we showed that tumors from patients who achieved a durable clinical response displayed a permissive microenvironment, substantiated by the upregulation of transcripts encoding for molecules involved in leukocyte adhesion and migration, cytotoxic functions, and antigen presentation. In responding patients, Imiquimod triggered a strong T-helper-1 (Th-1)/cytotoxic immune response, characterized by the coordinated upregulation of Th-1 chemokines, migration of Th-1 and cytotoxic T cells into the tumor, and activation of immune-effector functions, ultimately mediating tumor destruction. In conclusion, we have shown that topical imiquimod can induce a robust immune response in breast cancer metastases, and this response is more likely to occur in tumors with a pre-activated microenvironment. In this setting, imiquimod could be utilized in combination with other targeted immunotherapies to increase therapeutic efficacy.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders diseases & disorders > neoplasms diseases & disorders > cancer > cancer types > breast cancer organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions diseases & disorders > cancer > drugs and therapies > Immunotherapy organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte diseases & disorders > cancer > metastasis organs, tissues, organelles, cell types and functions diseases & disorders > cancer > cancer types
CSHL Authors:	Egeblad, Mikala
Communities:	CSHL labs > Egeblad lab CSHL Cancer Center Program > Cellular Communication in Cancer Program
Depositing User:	Matthew Dunn
Date:	12 June 2019
Date Deposited:	22 Jul 2019 16:58
Last Modified:	02 Feb 2024 20:27
PMCID:	PMC6561945
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/38171

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