Journal article
S. Mont, Kevin Black, Sheau-Chiann Chen, G. Ayers, A. Richmond, A. Vilgelm
Clinical Research (Excluding Clinical Trials), 2018
Clinical Research (Excluding Clinical Trials), 2018
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APA
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Mont, S., Black, K., Chen, S.-C., Ayers, G., Richmond, A., & Vilgelm, A. (2018). Abstract 607: Inhibition of CDK4/6 and Pi3Kγ modulates mammary tumor immune microenvironment to enhance response to immunotherapy. Clinical Research (Excluding Clinical Trials).
Chicago/Turabian
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Mont, S., Kevin Black, Sheau-Chiann Chen, G. Ayers, A. Richmond, and A. Vilgelm. “Abstract 607: Inhibition of CDK4/6 and Pi3Kγ Modulates Mammary Tumor Immune Microenvironment to Enhance Response to Immunotherapy.” Clinical Research (Excluding Clinical Trials) (2018).
MLA
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Mont, S., et al. “Abstract 607: Inhibition of CDK4/6 and Pi3Kγ Modulates Mammary Tumor Immune Microenvironment to Enhance Response to Immunotherapy.” Clinical Research (Excluding Clinical Trials), 2018.
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@article{s2018a,
title = {Abstract 607: Inhibition of CDK4/6 and Pi3Kγ modulates mammary tumor immune microenvironment to enhance response to immunotherapy},
year = {2018},
journal = {Clinical Research (Excluding Clinical Trials)},
author = {Mont, S. and Black, Kevin and Chen, Sheau-Chiann and Ayers, G. and Richmond, A. and Vilgelm, A.}
}
Abstract
An antitumor immune response is critical in achieving immunotherapy-driven tumor regression. Despite remarkable clinical advances in immunotherapies, patients with breast cancer have been only moderately responsive. In this study, we tested whether CDK4/6 inhibition in combination with Pi3Kγ inhibition can augment the immunotherapy response. Tumor growth was inhibited in the MMTV-PyMT breast cancer model when treated with palbociclib (CDK4/6i) in combination with anti-CD137, an antibody agonist of T cell co-stimulatory receptor 4-1BB. We also assessed the effect of palbociclib alone in a postsurgical model, where treatment began 5 days after injecting 37,000 MMTV-PyMT cells into the mammary fat pad, and show a significant inhibition of both average tumor weight and volume. In addition, we demonstrate that palbociclib can be effective in reducing total tumor burden in the PyMT-FVB spontaneous breast cancer model. Furthermore, mice treated with palbociclib in this model had an increase in CD3+ cell infiltrate in tumor lung metastasis. We used the Pi3Kγ-null mice treated with palbociclib or vehicle control to assess the effect of dual inhibition of CDK4/6 and Pi3Kγ on MMTV-PyMT tumors. We found an increase in CD45+ cells within the tumor microenvironment and an increase in MHC class II+, antigen-presenting macrophages upon palbociclib treatment. Additionally, gene expression analysis of chemokines in palbociclib-treated MCF-7 cells showed an increased expression of CCL4, CCL5, CXCL9, CXCL10, and CXCL11, each of which is implicated in T-cell tumor-homing. Overall, our results suggest that dual inhibition of CDK4/6 and Pi3Kγ may enhance tumor immunogenicity. Drugs targeting CDK4/6 and Pi3Kγ are of high clinical relevance and our findings indicate that they may be used in combination with immunotherapies for the treatment for breast cancer. Citation Format: Stacey Mont, Kevin Black, Sheau-Chiann Chen, Gregory D. Ayers, Ann Richmond, Anna E. Vilgelm. Inhibition of CDK4/6 and Pi3Kγ modulates mammary tumor immune microenvironment to enhance response to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 607.
