Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer

Journal of Ovarian Research

卷:11

Patrick J. Stiff¹  Maureen L. Drakes¹  M. Sharon Stack²  Yueying Liu²  Anne Grisoli²  Timothy E. O’Brien³  Ronald K. Potkul⁴  Swati Mehrotra⁵  Monica Aldulescu⁵  Cara Joyce⁶ 

[1] Cardinal Bernardin Cancer Center, Oncology Research Institute, Department of Medicine, Loyola University Chicago;

[2] Department of Chemistry & Biochemistry, Harper Cancer Research Institute, University of Notre Dame;

[3] Department of Mathematics & Statistics, and Institute of Environmental Sustainability, Loyola University Chicago;

[4] Department of Obstetrics and Gynecology, Loyola University Chicago;

[5] Department of Pathology, Stritch School of Medicine, Loyola University Chicago;

[6] Department of Public Health Sciences, Loyola University Chicago;

关键词: Programmed cell death-1;    Programmed cell death-1 ligand;    High grade disease;    Cancer immunotherapy;    Ovarian cancer;   

DOI  :  10.1186/s13048-018-0414-z

来源: DOAJ

【 摘 要 】

Abstract Background Ovarian cancer is the major cause of death among gynecologic cancers with 75% of patients diagnosed with advanced disease, and only 20% of these patients having a survival duration of five years. Treatments blocking immune checkpoint molecules, programmed cell death (PD-1) or its ligand PD-ligand- I (PD-L1) have produced a beneficial and prolonged effect in a subgroup of these patients. However, there is debate in the literature concerning the prognostic value of the expression of these molecules in tumors, with immunotherapy responsiveness, and survival. We evaluated the immune landscape of the ovarian tumor microenvironment of patients, by measuring the impact of the expression of tumor PD-1, PD-L1 and infiltrating lymphocytes on stage and grade of tumors and survival, in a cohort of 55 patients with gynecologic malignancies. Most patients under study were diagnosed with advanced disease ovarian cancer. Results Our studies revealed that a low density of PD-1 and of PD-L1 expressing cells in tumor tissue were significantly associated with advanced disease (P = 0.028 and P = 0.033, respectively). Moreover, PD-L1 was expressed significantly more often in high grade tumors (41.5%) than in low grade tumors of patients (7.7%) (P = 0.040). The presence of CD3 or of FoxP3 infiltrating cells with PD-L1 in patient tumors did not impact the significance of the association of PD-L1 with high grade tumors (P = 0.040), and our analyses did not show an association between the presence of PD-1 or PD-L1 and survival. Conclusions We conclude that a subgroup of advanced disease ovarian cancer patients with high grade tumors, expressing PD-L1, may be prime candidates for immunotherapy targeting PD-1 signaling.

【 授权许可】

Unknown