The David Healy Award for best Scientific Abstract was presented to Marcela Haro at the closing ceremony of the 15th World Congress on Endometriosis for her work on how Heterogeneous Immune Responses Underlie Subtype-Specific and Patient-Specific Heterogeneity in Endometriosis.
Haro M1,2, Fonseca M1,2, Abbasi F1,2, Goodridge H3,4, Siedhoff M5, Jefferies C6, Truong M5, Wright K5, Anglesio M 7,8, Medeiros F9, Lawrenson K1,2,10,11, Yu P10,2
1Women’s Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, United States of America, 2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center , Los Angeles, United States of America, 3Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America, 4Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, United States of America, 5Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, United States of America, 6 Department of Medicine, Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, United States of America, 7 Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada, 8British Columbia’s Gynecological Cancer Research (OVCARE) Program, University of British Columbia, Vancouver General Hospital, and BC Cancer, Vancouver, Canada, 9Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America, 10Cancer Prevention and Control Program, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, United States of America, 11Center for Bioinformatics and Functional
Genomics, Cedars-Sinai Medical Center, Los Angeles, United States of America
Introduction:
Endometriosis is characterized by endometrial-type glands and stroma growing outside of the uterine cavity, evading the typical cell-intrinsic and cell-extrinsic safeguards (including immune surveillance) that should prevent cells from surviving at ectopic locations. Chronic inflammation and dysregulation in the immune response contribute to the pathogenesis of endometriosis, however, little is understood regarding how immune dysregulation contributes to the extensive heterogeneity that characterizes endometriosis.
Aim:
This research seeks to phenotype the immune repertoire in endometriosis and explore the dysregulation in the molecular signals in the tissue microenvironment that influences immune cell recruitment and function.
Materials and Methods:
Single cell RNA sequencing was applied to >370,000 cells from endometriosis, eutopic endometrium, unaffected ovary and endometriosis-free peritoneum. All specimens were subjected to pathology review and genotyping for somatic variants in commonly mutated genes.
Results:
Endometriosis patients could be stratified into ‘immune-hot’ or ‘immune-cold’ subgroups based on the presence of lymphoid aggregates and germinal centers proximal to lesions. B-cells and plasma cells were particularly enriched in endometriosis. Elevated autoreactive antibodies, B-cell survival and recruitments signals and an interferon signature are seen in endometriosis.
Conclusion and impact:
Extensive heterogeneity in immune responses to endometriosis may explain, at least in part, the heterogenous presentations and symptoms associated with disease. Ongoing experiments are exploring the therapeutic potential of the anti-CD20 monoclonal antibody for patients with elevated B-cell dysfunction. This research is providing clinically relevant insights into the role of B-cells in the pathogenesis of endometriosis and potential targets for both diagnosis and therapeutics.