Abstract B021: Aneuploidy-associated cohesin RAD21 gains promote immune evasion in prostate cancers

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Abstract Aneuploidy, characterized by imbalanced chromosome numbers, is a hallmark of cancer and is strongly correlated with lethal progression in prostate cancer. Our recent work identified that gains of chromosome 8q, the most frequently gained chromosome in aneuploidy prostate cancers, drive cancer progression, partially through the cohesin RAD21 gene located on the chr8q24 region. We demonstrated that increased RAD21 expression accelerates lethal progression and oncogenesis in both prostate cancer and Ewing sarcoma by alleviating oncogenic stress during early-stage oncogenesis in both cell line and organoid models. Therefore, we hypothesize that elevated RAD21 levels could enable cancer cells to evade immune surveillance by mitigating oncogenic stress and DNA damage. In this study, we developed isogenic prostate and breast cancer cell culture models with varying levels of RAD21. Using a natural killer (NK) cell co-culture assay, we observed that cells with elevated RAD21 expression were significantly less susceptible to NK-mediated cytotoxicity and exhibited increased survivorship when co-cultured with NK cells. These findings align with publicly available data showing that tumors with high RAD21 levels have reduced NK cell infiltration in prostate cancer. Our results suggest that increased RAD21 expression, commonly associated with chr8q gains, facilitates immune evasion in cancer cells, thereby promoting early-stage oncogenesis. Understanding the role of RAD21 in immune evasion could reveal novel therapeutic strategies targeting immune surveillance mechanisms in prostate cancer. Citation Format: Elise G. DeArment, Ruoxi W. Wang, Kate Lu, Xiaofeng A. Su, Andrew Elliott, Nicholas A. Zorko, Justin H. Hwang, Xiaofeng A. Su. Aneuploidy-associated cohesin RAD21 gains promote immune evasion in prostate cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B021.

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