Abstract 2744: The immune landscape of recurrent ovarian carcinoma
Authors: Han T. Cun, Sammy Ferri-Borgogno, Rita Cheng, Jae-hoon Kim, Gwan Hee Han, Jared K. Burks, Karen H. Lu, Samuel C. Mok
Journal: Cancer Research (2021)

Abstract By examining the immune landscape in recurrent ovarian carcinoma, we can characterize the evolution of the tumor immune microenvironment (TIME) to understand its disease progression and response to therapy. Thus, the objective of this study is to evaluate the differences in the TIME in primary HGSOC compared to recurrent disease by utilizing imaging mass cytometry (IMC). Treatment naive primary HGSOC along with matched first recurrence tumors from the same patient were collected under an IRB-approved protocol. Formalin fixed paraffin embedded tissue sections were stained with 18 metal-tagged antibodies to detect various cell specific and immune related markers using the Fluidigm protocol. IMC data was obtained by the Fluidigm Helios CyTOF instrument utilizing the Hyperion Imaging System laser ablation module. Images from a 1mm2 area of each tissue section were processed and converted to tiff files using MCD Viewer (Fluidigm). Multiplex image analysis was performed with Visiopharm software, where tumor and stromal areas were separated based on presence or absence of Keratin 8/18, Collagen-I, and SMA respectively. Cells boundaries were determined by a pretrained Artificial Intelligence algorithm and phenotyped by Visiopharm unbiased autoclustering module using only the top 20% of pixel values per cell. Statistical analysis was performed using wilcoxon signed-rank test between cell densities of the primary and paired recurrent tumors. Paired primary and recurrent HGSOC samples were assessed from 27 patients. Stage of disease ranged from I to IV, but most were stage III (81.5%). The median time to first recurrence was 28 months (IQR 34). The image analysis showed that recurrent tumors had a lower density of stromal CD8a+ (p&amp;lt;0.01), CD8+granzymeB+CD45RO+, (p&amp;lt;0.01) and CD8+granzymeB+CD44+CD45RO+ cells (p&amp;lt;0.01) compared to primary tumors. Both stromal and intratumoral CD20+ cells were higher in recurrent tumors (p=0.03, p&amp;lt;0.01). Stromal CD73+Coll-I+ cells were lower in recurrent tumors (p&amp;lt;0.01). Our study demonstrates the evolution of the TIME of HGSOC from primary tumor to first recurrence. Recurrent tumors demonstrated lower stromal CD8+ T cells, specifically activated memory T cells and resting memory T cells, compared to their primary tumors, suggesting a more immunosuppressive environment. Although recurrent tumors had a higher density of CD20+ B cells, their function was not further described. These alterations propose that recurrent HGSOC demonstrates a more suppressive TIME that warrants further characterization. Citation Format: Han T. Cun, Sammy Ferri-Borgogno, Rita Cheng, Jae-hoon Kim, Gwan Hee Han, Jared K. Burks, Karen H. Lu, Samuel C. Mok. The immune landscape of recurrent ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2744.