Abstract 1701: Single-cell multi-omic profiling and clonal tracing of the human gynecological tumor microenvironment

Abstract

Abstract Tumor initiation and progression are the result of a close interplay between malignant cells and immune cells. While single-cell genomics has enabled the molecular dissection of the cellular heterogeneity underlying complex cancers, many facets of tumor microenvironments remain unresolved. In particular, the ontogeny of myeloid cells have not been fully understood in human tumors, although the source and expansion of macrophages have been suggested to underlie tumor development and metastasis in mice. In an effort to comprehensively characterize these tumor microenvironments, we profiled endometrial, ovarian, and metastatic tumors from 16 patients using CITE-seq (an atlas of 258,810 cells) and mitochondrial single-cell ATAC-seq (mtscATAC-seq; consisting of 173,820 cells). Our multi-omic analyses reveal the heterogeneity of tumor-infiltrating immune cells at clonal, epigenetic, transcriptomic, and proteomic levels. Notably, all tumor types harbored diverse exhausted T cell subsets, including terminal and precursor exhausted T cells, and gamma/delta T cells. Clonal somatic variant analysis between tumor tissues and peripheral blood mononuclear cells identified blood-derived monocytes, rather than embryonically derived cells, as the origin of macrophages within gynecological tumors. Further, our analyses show that macrophages expand minimally within the tumor microenvironment, suggesting that they may be continuously replenished by blood, an observation that may facilitate new approaches for cancer immunotherapy. In total, our dataset represents the first multi-modal single cell atlas of gynecologic tumors and reveals distinct features of T cell heterogeneity and myeloid expansions in complex tumor microenvironments. Citation Format: Vincent Liu, Katalin Sandor, Bence Daniel, Lionel Berthoin, Shan Sabri, Sofia Panagiotopoulou, Yajie Yin, Kamir Hiam-Galvez, Rene Sit, Zi Fan, Brendan Galvin, Omar Khan, Natalie Bezman, Jane Grogan, Brooke Howitt, Grace Zheng, Caleb Lareau, Ansuman Satpathy. Single-cell multi-omic profiling and clonal tracing of the human gynecological tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1701.