Figure 1.

Approach to profiling immune dysregulation in endometriosis and ovarian cancer. Endometrioid, clear cell and low grade serous ovarian tumors may develop from endometriosis, a chronic benign inflammatory condition consisting of endometrial-like epithelial glands (ovals) surrounded by immune stroma (circles). Atypical endometriosis (defined by morphological criteria) is considered to be the immediate cancer precursor. We recently profiled the immune microenvironment in normal endometrium, benign and atypical endometriosis and endometriosis-associated ovarian cancer (EAOC). Our results show that (1) while some of the atypical endometriosis cases have signs of benign inflammation (blue arrow), (2) 85% of cases have a cancerlike immune gene signature (red arrow). (3) Pathway analyses revealed complement activation and humoral immunity in endometriosis and EAOC. In parallel, mechanistic studies in ovarian cells from genetically engineered mice show that complement upregulation in epithelial cells does not trigger antibody-induced and complement-mediated cytotoxicity. Moreover, downregulation of complement inhibits tumor cell proliferation.