Abstract
Abstract Triple Negative Breast Cancer (TNBC) is a BC subgroup with the least favorable outcome and limited therapeutic options. Chemotherapy has long been the standard treatment, but resistance often develops. In recent years, various immunotherapy approaches have diversified, including combinations of chemo and immunotherapies. Increased understanding on how the difference in chemosensitivity affects the immune cells is of importance for further development of chemo-immunotherapies for TNBC. In this project we investigate how TNBC with distinct chemosensitivity modulate the immune microenvironment. Specifically, we explore the influence of the secretome, derived from the chemoresistant versus the sensitive BC cells, on macrophages (MØs) and T-cells. We have disclosed the chemosensitivity-dependent differences in the secretome, which were associated with diverse effects on MØ recruitment, polarization, and activation. Currently we investigate the secretome influence on interferon (IFN)-activated MØ. IFN stimuli is known to trigger tumoricidal activities in MØ, and we are setting up a co-culture assay, where such MØ functions could be explored in vitro. To study the secretome influence on T-cells, we employ T cell receptor (TCR)-engineered T cells that become activated in the presence of target cells. The preliminary results indicate that activation of the TCR T-cells was reduced in the presence of the “chemoresistant” secretome, suggesting its immunosuppressive influence. Work is in progress to validate this observation using other TCR T cells and functional markers of active T cells. Citation Format: Eleni Skourti, Kotryna Seip, Eivind V. Egeland, Shakila Jabeen, Nadia Mensali, Inger Øynebråten, Siri Juell, Else M. Inderberg, Olav Engebråten, Alexandre B. Corthay, Gunhild M. Mælandsmo, Lina Prasmickaite. Breast cancer with different chemosensitivity has distinct influence on the immune microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5554.
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