Humanized mouse models of triple-negative and triple-positive breast cancer for preclinical validation of novel immuno-oncology therapies

      Background: Immunotherapy has provided promising results in the treatment of breast cancer but there is a high variability in response between different subtypes. Triple-negative breast tumors have a high number of tumor infiltrating lymphocytes (TILs) and give good response to immunotherapy. On the contrast, hormone receptor positive breast tumors attract less immune cells and are less sensitive to immunotherapy. Based on the immune attractive phenotype these tumors are referred as “hot” and “cold” tumors. Independently from the breast cancer subtype, the patients typically develop bone metastases in high frequency. Bone metastases are incurable and novel immunotherapies hold the potential to treat patients with bone metastatic disease. Up to recent years, preclinical validation of efficacy of immunomodulators has been limited to the use of syngeneic models. To shorten the cap in clinical translation, humanized mouse models with functional human immune system have been developed. The aim of this study was to establish two different preclinical breast cancer models in humanized mice to be used in the preclinical evaluation of new immunotherapies in bone metastatic setting.
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