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
2743 - The Impact of Targeted Therapies and Immunotherapy in Melanoma Brain Metastases: a Systematic Review and Meta-Analysis
Presenter: Mario Mandala
Session: Poster Display session 3
Resources:
Abstract
5479 - Intracranial Anti-Tumor Activity in Melanoma Brain Metastases with Encorafenib Plus Binimetinib: A Multicenter, Retrospective Analysis
Presenter: Jose Lutzky
Session: Poster Display session 3
Resources:
Abstract
3560 - Outcomes of Patients with Melanoma Brain Metastases (MBM) Treated with Standard of Care Therapy After Being Excluded from MBM-Specific Clinical Trials
Presenter: Kourtney Holbrook
Session: Poster Display session 3
Resources:
Abstract
3175 - The analysis of current treatment outcomes in melanoma patients with brain metastases
Presenter: Joanna Placzke
Session: Poster Display session 3
Resources:
Abstract
4550 - A multivariate model to define prognostic groups among patients with melanoma brain metastases: a 10-year retrospective cohort study
Presenter: Giacomo Pelizzari
Session: Poster Display session 3
Resources:
Abstract
4191 - The immune landscape of melanoma significantly influences survival in patients with highly mutated tumors.
Presenter: Robert Ferguson
Session: Poster Display session 3
Resources:
Abstract
1625 - Final Results from Phase II of Combination with Canerpaturev (formerly HF10), an Oncolytic Viral Immunotherapy, and Ipilimumab in Unresectable or Metastatic Melanoma in 2nd-or later line treatment
Presenter: Kenji Yokota
Session: Poster Display session 3
Resources:
Abstract
5346 - Evaluating polygenic risk score prediction model for melanoma prognosis
Presenter: Miriam Potrony
Session: Poster Display session 3
Resources:
Abstract
5477 - Impact of sarcopenia in patients with metastatic melanoma treated with immunotherapy
Presenter: Maria Grazia Vitale
Session: Poster Display session 3
Resources:
Abstract
3469 - Ancillary evaluation of systemic immune antitumor response (SIAR) and tumor growth rate (TGR) of patients (pts) with metastatic melanoma (MM) treated with radiotherapy (RT) combined with ipilimumab (ipi) in the phase 1 study Mel-Ipi-Rx.
Presenter: Celine Boutros
Session: Poster Display session 3
Resources:
Abstract