Abstract 3919
Background
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.
Methods
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.
Results
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).
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hellenic Cooperative Oncology Group (HeCOG).
Funding
Hellenic Cooperative Oncology Group (HeCOG).
Disclosure
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.
Resources from the same session
1694 - Pembrolizumab (pembro) Plus mFOLFOX or FOLFIRI in Patients With Metastatic Colorectal Cancer (mCRC): KEYNOTE-651 Cohorts B and D
Presenter: Richard Kim
Session: Poster Display session 2
Resources:
Abstract
908 - Romidepsin (FK228) Regulates the Expression of the Immune Checkpoint Ligand PD-L1 and Exerts Synergistic Anti-Tumor Activity with an Anti-PD-1 Antibody in Colon Cancer
Presenter: Hui Li
Session: Poster Display session 2
Resources:
Abstract
3127 - Prognostic significance of circulating regulatory T lymphocytes (Tregs) in patients with metastatic colorectal cancer (mCRC) under treatment with first line chemotherapy.
Presenter: Zafeiris Zafeiriou
Session: Poster Display session 2
Resources:
Abstract
5416 - The SAFFO study: Sex-related prognostic role And cut-oFf deFinition of monocyte-to-lymphocyte ratio (MLR) in metastatic colOrectal cancer
Presenter: Camilla Lisanti
Session: Poster Display session 2
Resources:
Abstract
2518 - SPICE, a phase I study of enadenotucirev in combination with nivolumab in tumors of epithelial origin: analysis of the metastatic colorectal cancer patients in the dose escalation phase
Presenter: Marwan Fakih
Session: Poster Display session 2
Resources:
Abstract
4000 - Phase 1/2 study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer
Presenter: Niels Halama
Session: Poster Display session 2
Resources:
Abstract
2223 - Microsatellite Instability Status in Metastatic Colorectal Cancer and Effect of Immune Checkpoint Inhibitors on Survival in MSI-High Metastatic Colorectal Cancer
Presenter: Wataru Okamoto
Session: Poster Display session 2
Resources:
Abstract
2569 - Phase II trial of Trametinib (T) and Panitumumab (Pmab) in RAS/RAF wild type (wt) metastatic colorectal cancer (mCRC)
Presenter: Kanan Alshammari
Session: Poster Display session 2
Resources:
Abstract
5402 - Microsatellite instability and immunogenicity in colorectal cancer – do resident memory Tcells (Trm) play a role in colorectal cancer
Presenter: Wei Toh
Session: Poster Display session 2
Resources:
Abstract
5472 - Early response evaluation and CEA response in patients treated in a Danish randomized study comparing trifluridine/tipiracil (TAS-102) with or without bevazicumab in patients with chemorefractory metastatic colorectal cancer (mCRC)
Presenter: Camilla Qvortrup
Session: Poster Display session 2
Resources:
Abstract