Objectives:
T-cell suppression via PD-1/PD-L1 interactions plays a central role in cancer progression and survival, making PD-1/PD-L1 attractive therapeutic targets. Clinical trials involving PD-1/PD-L1-targeted immunotherapies have demonstrated marked success in solid tumors including melanoma, non-small cell lung carcinoma (NSCLC), and renal cell carcinoma, and studies indicate PD-L1 expression may identify patients who are more likely to benefit from immunotherapies. These agents and biomarkers could revolutionize management of gynecological malignancies that have developed resistance to standard chemotherapies. The purpose of this study is to identify gynecological malignancies that may benefit from this new class of targeted therapy.
Methods:
1599 cases encompassing all gynecological malignancies (e.g. cervical, uterine, ovarian, vaginal, vulvar) were evaluated at a central laboratory (Caris Life Sciences) for the presence of PD-1 (NAT105) and PD-L1 (B7-H1 antibody) expressing cells. Intraepithelial PD-1-positive lymphocytes (IEL) and aberrantly expressed PD-L1 on carcinoma cells were considered specific.
Results:
Overall, positive PD-1 expression was 67.9% (1086/1599) and PD-L1 expression was 19.6% (313/1598). Analysis showed the highest PD-1 expression in the following tumor types: endometrial cancer (337/450, 74.9%), epithelial ovarian cancer (622/930, 66.9%), and cervical cancer (53/84, 63.1%). Furthermore, the highest PD-L1 expression rates were in the following tumor types: ovarian sex cord – stromal tumors (24/32, 75.0%), uterine sarcoma (40/86, 46.5%), endometrial cancer (112/450, 24.9%). In terms of histology, the highest PD-1 expression rates were in carcinosarcomas of the endometrium and ovary (80.0% and 74.2%, respectively) while the highest PD-L1 expression rates occurred in granulosa cell tumors (77.8%) and endometrioid endometrial cancer (39.7%). Amongst the highest PD1/PD-L1 co-expression rate was in endometrioid endometrial cancer (35.3%).
Conclusions:
Subsets of gynecological cancer preferentially express PD1 and PD-L1, implying potential application of a new set of agents in the treatment of gynecological cancers. As no predictive standard exists, biomarker studies will be necessary to elucidate which patients derive the most benefit from novel immunotherapies.