Abstract 3174: Spatial immune cell and transcriptome profiling of tumors from primary and metastatic sites in advanced uterine serous carcinoma patients

Abstract

Abstract Uterine serous carcinoma (USC) is a rare but the most aggressive subtype of endometrial cancer (EC) that represents less than 10% of all cases but contributes to more than 40% of EC related deaths. The low 5-year overall survival (OS) rate and high lethality of USC patients are mainly caused by aggressive extra-uterine metastasis frequently to lymph nodes and omentum. Deeply understanding the underneath mechanism that leads to USC progression is essential for the development of therapeutic strategies for USC patients. The communication between tumor and different subpopulations of immune cells has been widely proven to determine tumor cells fate and plays critical role during tumor proliferation and metastasis. Given the immunological study in USC still much lags behind other cancer types, the purpose of this study is to use tumors collecting from primary and metastatic sites in USC patients to demonstrate the role of immune cell landscape and associated molecular signaling networks in USC progression. Formalin fixed embedded (FFPE) tissue sections from both primary and metastasis sites (lymph node metastasis) of 12 USC patients were used. A panel of 6 reactive fluorophores, spectral DAPI together with functional markers granzyme B and Ki-67 were used to examine the spatial localization of a variety of tumor-infiltrating immune cells by multiplex immunofluorescence IHC assay using OpalTM immunology detection kit. Images were acquired by a Vetra 3.0 microscope and data analysis was performed by the VisioPharm software and bioinformatics tools. Transcriptome analyses were performed on RNA isolated from microdissected tumor cells the human Clariom D transcriptomics assay. Transcriptome Analysis Console was employed to identify altered differential genes and signaling pathways between primary tumor and metastatic sites. The primary and metastatic USC displayed quite distinct immune landscapes suggesting the essential role of immune system during metastasis. Primary sites contained markedly higher density of intratumoral activated tumor-infiltrating cytotoxic T cells (CD8+granzyme B+), and CD8+LCK+ T cell subpopulation than the metastatic sites in lymph nodes. In addition, we found that the density and spatial distribution of activated CD8+ T cells positively correlated with the overall survival of USC patients. Transcriptome analyses demonstrated that 781 of upregulated genes with fold > 2, p <= 0.05 were identified in tumor cells in primary sites compared to metastatic sites. Furthermore, multiple signaling pathways associated with immune cell activation and tumor cell metastasis were also found to be enriched in primary sites. Our study suggests that distinct immune cell landscapes and molecular signaling networks in the lymph nodes provide a permissive niche that support USC progression, which may lead to poor survival rates in patients with advanced USC. Citation Format: Li Zhang, Angela Rynne-Vidal, Karen H Lu, Samuel C Mok. Spatial immune cell and transcriptome profiling of tumors from primary and metastatic sites in advanced uterine serous carcinoma patients [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 3174.