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
5389 - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): final results of phase II trial.
Presenter: Alexey Tryakin
Session: Poster Display session 3
Resources:
Abstract
2934 - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy
Presenter: Lucia Nappi
Session: Poster Display session 3
Resources:
Abstract
3585 - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)
Presenter: Esmeralda Garcia Torralba
Session: Poster Display session 3
Resources:
Abstract
2254 - The Effects Of Primary Testicular Tumor Localization On Prognosis In Patients With Nonseminomatous Testis Cancer
Presenter: Birol Yildiz
Session: Poster Display session 3
Resources:
Abstract
4505 - Initial Results of a Phase II study of Nivolumab and Ipilimumab in Metastatic Adrenal Tumors.
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
3369 - NEMIO: a randomized phase II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma
Presenter: Constance Thibault
Session: Poster Display session 3
Resources:
Abstract
2075 - KEYNOTE-866: Phase 3 Study of Perioperative Pembrolizumab (pembro) or Placebo (pbo) in Combination With Neoadjuvant Chemotherapy in Cisplatin (cis)-Eligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
4824 - KEYNOTE-905: A Phase 3 Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin (cis)-Ineligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Matthew Galsky
Session: Poster Display session 3
Resources:
Abstract
2253 - Phase 3 LEAP-011 trial: First-Line Pembrolizumab With Lenvatinib in Patients With Advanced Urothelial Carcinoma Ineligible to Receive Platinum-Based Chemotherapy
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).
Presenter: Noemie Gassian
Session: Poster Display session 3
Resources:
Abstract