Abstract B65: MetaTiME: meta-components of the tumor immune microenvironment

Abstract Recent advances in single-cell RNA sequencing have revealed heterogeneous cell types and gene expression states in the non-cancerous cells in tumors. The integration of multiple scRNA-seq datasets across tumors can reveal common cell types and states in the tumor microenvironment (TME). However, tumor scRNA analysis relies on clustering cells and annotating with markers from experts. Subsequent challenges include inconsistent cell type and state definition, different marker usage among studies, and that clustering doesn’t find continuous cell states. We developed a data-driven framework, MetaTiME, to overcome the limitations in resolution and consistency that result from manual labeling using known gene markers. Using millions of TME single cells, MetaTiME learns meta-components that encode independent components of gene expression observed across cancer types. The meta-components are biologically interpretable as cell types, cell states, and signaling activities. For example, the T cell co-signaling meta-component reflects co-expressed gene modules of multiple immune checkpoint blockade targets. Also, the tumor-infiltrating macrophage meta-components found macrophage states in different metabolism preferences, rather than the pro-inflammatory versus anti-inflammatory classifications. We also observed certain macrophage states associated with tumor prognosis and cancer immunotherapy response. By projecting onto the MetaTiME space, we provide a tool to annotate cell states and signature continuums for TME scRNA-seq data. Lastly, leveraging epigenetics data, MetaTiME reveals critical transcriptional regulators for the cell states. Overall, MetaTiME learns data-driven meta-components that depict cellular states and gene regulators for tumor immunity and cancer immunotherapy. Citation Format: Yi Zhang, Guanjue Xiang, Yijia Alva Jiang, Allen Lynch, Zexian Zeng, Chenfei Wang, Wubing Zhang, Jingyu Fan, Jiajinlong Kang, Shengqing Gu, Changxin Wan, Boning Zhang, Shirley Liu, Myles Brown, Clifford Meyer. MetaTiME: meta-components of the tumor immune microenvironment [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B65.