Abstract PO011: Spatial immune cell and transcriptome profiling uncover differential cellular and molecular signatures in primary and metastatic tumor sites in patients with advanced uterine serous cancer

Abstract

Abstract Uterine serous carcinoma (USC) is the most aggressive and lethal subtype of endometrial cancer with a low overall patient survival rate of 18%-27%. Extra-uterine metastasis is frequently found in lymph nodes and omentum. The high lethality and poor understanding of the underneath mechanisms that drives USC progression lead to an urgency to develop novel therapeutic tools for the treatment of USC patients. Metastasis is proven to be the leading cause of death from USC and the immune system plays a vital role for this process. However, differential cellular and molecular profiles in the primary and metastatic tumor microenvironment have not been thoroughly examined. To identify the immune cell profile of USC, a panel of 7 immune cell markers 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 (Perkin Elmer). Formalin fixed paraffin embedded (FFPE) tissue sections from both primary and metastasis sites (lymph node metastasis) of 10 USC patients were used. Vetra 3.0 microscope was used to take photos of stained slides. Images were quantified and analyzed by inForm software. Transcriptome profiling of microdissected tumor cells from the same tissue samples was performed using the human Clariom D assay platform. Our results demonstrated that primary USC sites had significantly higher density of intratumoral activated tumor-infiltrating cytotoxic T cells (CD8+granzyme B+), and CD8 and LCK double positive T cell subpopulation (CD8+LCK+) than the metastatic sites in lymph nodes. In addition, we found that the density and spatial distribution of activated CD8+ T cells correlate with the overall survival of USC patients. Furthermore, differentially expressed genes and signaling networks associated immune cell activation and tumor cell metastasis were identified in primary sites compared with those in the metastatic sites. Taken together, our study suggested that the immune cell and molecular phenotypes in the lymph nodes provide a permissive niche that support USC progression, which may lead to poor survival rates in patients with advanced USC. Targeting these altered signaling networks may provide novel therapeutic strategies in the treatment of USC patients. Citation Format: Li Zhang, Angela Rynne-Vidal, Karen H. Lu, Samuel C. Mok. Spatial immune cell and transcriptome profiling uncover differential cellular and molecular signatures in primary and metastatic tumor sites in patients with advanced uterine serous cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO011.