The characterization of the adaptive immune landscape in epithelial ovarian cancer (EOC) is of paramount importance for the stratification of patients (pts) for therapeutic interventions, especially in the context of immunotherapy.
In the present analysis pts with EOC and available tumor tissue were included. All pts had received treatment with platinum and paclitaxel.We evaluated elements of the adaptive immunity such as Tertiary Lymphoid Structures (TLS), plasma cells (PCs) and CD8+T cells, intraepithelial (iCD8) and stromal (sCD8), as well as p53 immunoexpression. Assessment of TLS (presence, absence) and PCs (4-tiered score) was performed in H&E stained whole tumor sections whereas of CD8 and p53 in IHC stained Tissue Microarrays (TMAs), constructed from the same tumor area. For iCD8, 5 cells/HPF was considered as the cut-off value for low vs high expression, whereas absolute absence of p53 expression or immunopositivity in > 60% of tumor cells was considered as p53 mutated by IHC (mIHCp53). Survival data have been retrieved from 613 patients.
From 04/1996 to 11/2016 687 pts were treated; median age was 58.8 years (range 21.7-84.4). Stage III disease was diagnosed in 431 (69.3%), while stage IV in 70 (11.3%) pts. Most tumors had absence of TLS (74.2%), 0-1 PCs score (78.7%), low iCD8 and sCD8 expression (75.4% and 50.3%) and mIHCp53 (73.6%). The presence of TLS correlated with high iCD8 and sCD8 expression and 2-3 PCs score (all p’s <0.001), but not with prognosis in this cohort (p = 0.99). The median OS was 71.9 months (95% CI 65.5-83.9). Age was an independent unfavorable prognosticator for OS (HR = 1.02, p < 0.001). Low iCD8 expression and mIHCp53 univariately conferred higher risk of death (HR = 1.42; p = 0.038 and HR = 1.54; p = 0.010, respectively). Upon multivariate analysis, low iCD8 expression retained its unfavorable prognostic significance for OS (HR = 1.54, p = 0.011), while a trend towards worse survival was detected for mIHCp53 (HR = 1.38, p = 0.062).
The presence of effector cells of adaptive immunity such as PCs and cytotoxic T cells correlated with the presence of TLS and was closely linked to clinical outcome in EOC.
Hellenic Cooperative Oncology Group (HeCOG).
Hellenic Cooperative Oncology Group (HeCOG).
E. Fountzilas: Shareholder / Stockholder / Stock options: Deciphera; Travel / Accommodation / Expenses: K.A.M Oncology / Hematology; Travel / Accommodation / Expenses: Merck. G. Pentheroudakis: Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Merck; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Roche; Advisory / Consultancy, Leadership role: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Lilly; Leadership role, Research grant / Funding (institution): Boehringer; Leadership role: Enorasis. G. Aravantinos: Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche Hellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Genesis Pharma; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer. G. Fountzilas: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche; Honoraria (self): AstraZeneca. All other authors have declared no conflicts of interest.