Abstract 849P
Background
Ovarian cancer (OC) is the most lethal of gynecological cancers with five-year survival rate of only ca. 45 %. The most common histologic subtype, high-grade serous carcinoma (HGSC), is typically presented with advanced stage and development of chemoresistance. Therefore, new treatment options, including immunotherapies, are needed. Understanding the features of the immune cell populations and their interaction in the tumor microenvironment (TME) is essential for developing personalized treatment options and finding predictive biomarkers. Digital image analysis (DIA) may enhance the accuracy and reliability of immune cell infiltration assessment in the TME. The aim of this study was to characterize TME in a retrospective cohort of high-grade serous ovarian cancer samples with whole-slide imaging (WSI) and digital image analysis (DIA).
Methods
Formalin-fixed paraffin-embedded (FFPE) HGSC tumor tissue samples (n=67) were analyzed for six different immunohistochemical (IHC) stainings: CD4, CD8, FoxP3, granzyme B, CD68 and CD163. The stained specimens were scanned into a digital format and assessed using QuPath 0.1.2. and ImageJ softwares. Staining patterns were associated with clinico-pathological and survival data.
Results
The higher amount of CD8+, CD163+ and granzyme B+ immune cells was associated with survival benefit analyzed individually, but high levels of both CD8+ and granzyme B+ TILs was an independent prognostic factor in Cox multivariate regression analysis (HR=0.287 for relapse, p=0.002). In addition, the given neoadjuvant chemotherapy (NACT) was associated with lower FoxP3+ TIL density (Fisher’s exact test, p=0.013).
Conclusions
Tumors having concomitant high amount of Granzyme B+ and CD8+ TILs showed better prognosis possibly reflecting an activated immune state in the TME. The combined positivity of CD8 and granzyme B warrants further investigation with respect to predicting response to immune therapy. NACT may have an effect on the TME and therefore on the response to immuno-oncologic or chemotherapy treatments.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.