Abstract 5392
Background
In HGSOC, the positive association between tumor-infiltrating lymphocytes (TILs) and survival suggests that immunotherapy might be beneficial. Despite this, initial attempts had limited efficacy. The pattern of IRs expression displayed by HGSOC TILs has not been fully determined. We characterized the phenotype of TILs in HGSOC to identify immunosuppressive pathways limiting anti-tumor T-cell activity.
Methods
Peripheral blood (PB), primary tumor and ascites were retrieved from HGSOC patients admitted for primary surgery in our Institute. Tumor immune infiltrate was characterized on 34 formalin-fixed paraffin-embedded specimens by immunohistochemistry (IHC) for lineage markers (CD20, CD3, CD8, CD4, CD163) and inhibitory molecules (PD-1, PD-L1, LAG-3, TIM-3, VISTA).T cells isolated from tumor, ascites and PB of 14 patients were also characterized by flow cytometry for the expression of lineage and memory markers (CD3, CD4, CD8, CD45RA, CD62L, CD95), inhibitory molecules (PD1, CTLA-4, LAG-3, TIGIT, TIM-3, 2B4, GITR, KLRG1, CD39, CD160) and the activation marker CD137.
Results
The entity of immune infiltration was heterogeneous: 2/34 of cases (6%) were immune desert; all other cases displayed a wide range of immune cell density, dominated by T lymphocytes and macrophages. B cells were scanty. Intratumoral T cells (ITTCs) were present in 30/34 cases (88.2%), almost constantly CD8. PD-1, LAG-3 and TIM-3 were expressed by 61.9%, 61.7% and 61.7% of ITTCs respectively. VISTA was rarely expressed. PD-L1 was expressed by neoplastic cells and immune cells (mainly macrophages) in 40% and 82.3% of samples, respectively. Flow cytometry confirmed the expression by TILs of several IRs (mainly PD-1, CD39, TIM-3 and LAG-3), with variable percentages of positive cells. Compared with corresponding PB and ascites, TILs were enriched in effector memory lymphocytes and in cells co-expressing PD-1, CD39 and CD137.
Conclusions
These data suggest that HGSOC is infiltrated by antigen-experienced T lymphocytes displaying features of both activation and partial exhaustion. The anti-tumor activity of such cells still needs to be determined.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
AIRC Associazione Italiana Ricerca sul Cancro.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5678 - Nanomaterials Augmented LDI-TOF-MS for Hepatocellular Carcinoma Diagnosis and Classification
Presenter: Jian Zhou
Session: Poster Display session 3
Resources:
Abstract
2436 - Development and Validation of an RNA-Seq Assay for Gene Fusions Detection in Formalin-Fixed Paraffin-Embedded Samples
Presenter: Hua Dong
Session: Poster Display session 3
Resources:
Abstract
5271 - A Pilot Study to Implement an Artificial Intelligence (AI) System for Gastrointestinal Cancer Clinical Trial Matching
Presenter: Zhaohui Jin
Session: Poster Display session 3
Resources:
Abstract
4787 - A Blinded Comparison of Patient Treatments to Therapeutic Options Presented by an Artificial Intelligence-based Clinical Decision-support system
Presenter: Suthida Suwanvecho
Session: Poster Display session 3
Resources:
Abstract
5744 - OncOS: scalable and accurate next-generation sequencing analytics for precision oncology and personalized patient care
Presenter: Joe Thompson
Session: Poster Display session 3
Resources:
Abstract
3752 - The association between wearable device physical activity metrics and performance status in oncology: a systematic review
Presenter: Milan Kos
Session: Poster Display session 3
Resources:
Abstract
5820 - SomaticNET: neural network evaluation of somatic mutations in cancer
Presenter: Geoffroy Dubourg-Felonneau
Session: Poster Display session 3
Resources:
Abstract
4771 - Is there a role for Next-generation sequencing (NGS) profiling on metastatic non-colorectal gastrointestinal carcinomas (MNCGIC) in developing countries? A single center experience.
Presenter: Mauricio Ribeiro
Session: Poster Display session 3
Resources:
Abstract
1209 - Metastatic Cancer Whole-Exome Sequencing in daily practice
Presenter: Manon Réda
Session: Poster Display session 3
Resources:
Abstract
5702 - Genomic-Guided Individualized Precision Therapy in Refractory Metastatic Solid Tumor Patients with Extensively Poor Performance Status: A Chinese single institutional prospective observational real-world study
Presenter: Haitao Wang
Session: Poster Display session 3
Resources:
Abstract