Fallopian tube single cell analysis reveals myeloid cell alterations in high-grade serous ovarian cancer

Joshua Brand; Marcela Haro; Xianzhi Lin; B J Rimel; Stephanie M McGregor; Kate Lawrenson; Huy Q Dinh

doi:10.1016/j.isci.2024.108990

Fallopian tube single cell analysis reveals myeloid cell alterations in high-grade serous ovarian cancer

iScience. 2024 Jan 23;27(3):108990. doi: 10.1016/j.isci.2024.108990. eCollection 2024 Mar 15.

Authors

Joshua Brand¹, Marcela Haro^{2

3}, Xianzhi Lin^{2

3

4}, B J Rimel^{2

3}, Stephanie M McGregor^{5

6}, Kate Lawrenson^{2

3}, Huy Q Dinh^{1

6

7}

Affiliations

¹ McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, WI 53705, USA.
² Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
³ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁴ RNA Biology Group, Division of Natural and Applied Sciences and Global Health Research Center, Duke Kunshan University, Kunshan 215316, Jiangsu Province, China.
⁵ Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, WI 53705, USA.
⁶ University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
⁷ Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, WI 53705, USA.

Abstract

Most high-grade serous ovarian cancers (HGSCs) likely initiate from fallopian tube (FT) epithelia. While epithelial subtypes have been characterized using single-cell RNA-sequencing (scRNA-Seq), heterogeneity of other compartments and their involvement in tumor progression are poorly defined. Integrated analysis of human FT scRNA-Seq and HGSC-related tissues, including tumors, revealed greater immune and stromal transcriptional diversity than previously reported. We identified abundant monocytes in FTs across two independent cohorts. The ratio of macrophages to monocytes is similar between benign FTs, ovaries, and adjacent normal tissues but significantly greater in tumors. FT-defined monocyte and macrophage signatures, cell-cell communication, and gene set enrichment analyses identified monocyte- and macrophage-specific interactions and functional pathways in paired tumors and adjacent normal tissues. Further reanalysis of HGSC scRNA-Seq identified monocyte and macrophage subsets associated with neoadjuvant chemotherapy. Taken together, our work provides data that an altered FT myeloid cell composition could inform the discovery of early detection markers for HGSC.

Keywords: Cancer; Immunology; Microenvironment; Transcriptomics.

Abstract

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