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Poster Display session 3

5392 - Activated effector T cells co-expressing multiple inhibitory receptors (IRs) are enriched in the tumor immune microenvironment in high grade serous ovarian cancer (HGSOC)


30 Sep 2019


Poster Display session 3


Translational Research

Tumour Site

Ovarian Cancer


Alice Bergamini


Annals of Oncology (2019) 30 (suppl_5): v760-v796. 10.1093/annonc/mdz268


A. Bergamini1, E. Tassi2, J. Wignall2, L. Bocciolone1, M. CANDIANI1, A. Potenza2, F. Manfredi2, G. TACCAGNI3, F. Scalisi3, C. Doglioni3, G. MANGILI1, C. Bonini2

Author affiliations

  • 1 Obstetrics And Gynecology, IRCCS Ospedale San Raffaele, 20132 - Milan/IT
  • 2 Experimental Hematology Unit, San raffaele Scientific Institute, 20132 - MILANO/IT
  • 3 Surgical Pathology, IRCCS Ospedale San Raffaele, 20132 - MILANO/IT


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Abstract 5392


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.


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.


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.


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.


AIRC Associazione Italiana Ricerca sul Cancro.


All authors have declared no conflicts of interest.

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