Disease Heterogeneity and Immune Biomarkers in Preclinical Mouse Models of Ovarian Carcinogenesis
Annual rept. 1 Aug 2013-31 Jul 2014
MAGEE-WOMEN'S HOSPITAL PITTSBURGH PA
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Human studies performed in yeas 3 and 4 led to the discovery of several immune genes that are differentially expressed in endometriosis, atypical endometriosis, endometriosis-associated ovarian cancer EAOC, endometrial and clear cell. Of these genes, complement pathway genes were consistently present, suggesting that complement-induced immunity may be involved in the pathogenic events during the transition from endometriosis to EAOC. In year 4, we have focused on immune gene signatures associated with response to immune therapy. Using our new transplantable ovarian cancer model in completely syngeneic immune competent mice, we tested in vivo the efficacy of anti- PDL1 antibody administered intraperitoneal IP. PD-L1 is a molecule in the immune checkpoint pathway. It binds to PD-1 receptor on T cells and induces inhibition of effector function of cytolytic T cells. Our results demonstrate that blocking the PD- 1PD-L1 interaction through IP administration of anti-PD-L1 antibody significantly increases survival and triggers upregulation of several immune genes associated with CD8 T cell function. Immune checkpoint blockade has been proven effective in recent clinical trials mostly in melanoma, lung and renal carcinomas. Our results provide strong support in its suitability in ovarian cancer.
- Medicine and Medical Research