W191 - Microenvironments of Malignant versus Non-malignant Metastases to the Gut

Arjun Modi – Immunology – Mayo Clinic; Alexey Leontovich, Ph.D. – Research Scientist, Biomedical Informatics, Mayo Clinic; Joseph Grande, M.D., Ph.D. – Emeritus, Laboratory Medicine and Pathology, Mayo Clinic; Svetomir Markovic, M.D., Ph.D. – Medical Oncology Consultant, Medical Oncology, Mayo Clinic; Zaraq Khan, M.B.B.S – Consultant, Obstetrics and Gynecology, Mayo Clinic; Rachel Maus – Ph.D., Oncology, Mayo Clinic; Valentin Carapanceanu – Research Assistant, Immunology, Mayo Clinic; Nicoleta Carapanceanu – Senior Research Technologist, Immunology, Mayo Clinic; Khashayarsha Khazaie, Ph.D. – Research Consultant, Immunology, Mayo Clinic

Abstract Text: Metastasis is the development of secondary malignant growths at a site distant from its origin. We used multiplex immunofluorescent staining and spatial analysis to compare metastatic endometrial cancer with endometriosis, a non-malignant metastasis. Using colon and small bowel disseminated specimens from 3 patients per disease, 90 fields of views (FOVs) per patient, and 37 fluorescence antibodies. Spatial analysis was performed to quantify the expression of cells and the composition of communication between leukocytes in endometriotic lesions versus endometrial carcinoma. Endometrial lesions are well-demarcated, consisting of glandular epithelial structures with strong expression of HLA-I in late endometriosis and expression of HLA-II in the initial stages. These lesions are active sites of antigen presentation between the early ectopic epithelium and T-cells and between professional CD206+HLA-II+ cells. Tertiary lymphoid follicles in endometriosis present themselves more frequently with distinct T-cell and B-cell zones more than twice as frequent and have a consistently higher incidence of contacts between T-cells, antigen-presenting cells, and B-cells versus endometrial carcinoma. By contrast, expression of HLA-I is sporadic in endometrial cancer metastases and has lower densities of CD206+HLA-II+ cells and contact with T-cells, indicative of lower immune activity. Surprisingly, T-cells have more frequent contact with tumor epithelial than ectopic endometrial cells. Our observations indicate differences in lesion morphology, expression of HLA by disseminated cells, infiltration by immune cells, formation of lymphoid follicles, and antigen presentation. These studies provide the rationale for the investigation of the epigenetic and gene expression programs by which disseminated cells contribute to shaping their immediate environment.