ESTRO 2023

Session Item

Immuno-radiobiology

Session Code: 8010

Session Type: Poster (Digital)

Track: Radiobiology

HDR-brachytherapy increases PD-L-1 immune expression on prostate cancer (NCT04247217)

, Belgium

Presentation Number: PO-2242

Abstract

Abstract Title:

HDR-brachytherapy increases PD-L-1 immune expression on prostate cancer (NCT04247217)

Authors:

Ben Vanneste^1,2, Evert Van Limbergen³, Ludwig Dubois⁴, Lotte Wieten⁵, Maureen Aarts⁶, Joep Van Roermund⁷, Tom Marcelissen⁸, Xiaofei Li⁹, Iryna Samarasks¹⁰, Dirk De Ruysscher¹

¹Maastro, Department of Radiation Oncology, Maastricht, The Netherlands; ²Ghent University Hospital, Department of Human Structure and Repair; Department of Radiation Oncology, Ghent, Belgium; ³MAASTRO, Radiation Oncology , Maastricht, The Netherlands; ⁴MUMC, M-Lab, Department of Precision Medicine, GROW , Maastricht, The Netherlands; ⁵MUMC, Department of Transplantation Immunology, Tissue Typing Laboratory, GROW School for Oncology and Developmental Biology, Maastricht, The Netherlands; ⁶MUMC, Department of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht, The Netherlands; ⁷MUMC, Department of Urolog, Maastricht, The Netherlands; ⁸MUMC, Department of Urology, Maastricht, The Netherlands; ⁹MUMC, Department of Pathology, , Maastricht, The Netherlands; ¹⁰MUMC, Department of Pathology, Maastricht, The Netherlands

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Purpose or Objective

Programmed cell death protein 1 (PD-1) is an inhibitory receptor that is expressed by all T cells during activation. The expression of the PD-1 receptor and its ligand, PD-(L)-1, is also observed in several solid cancers [1]. However, the expression levels as well as clustered T-cell infiltrates in prostate cancer are very low suggesting prostate cancer as an immune ‘’cold’’ tumor [2]. It has been suggested that radiotherapy might enhance PD-1 and PD-L-1 expression [3,4]. Our hypothesis is that an increased PD-L-1 is induced by high-dose-rate (HDR)-brachytherapy.

Material and Methods

Prospective study of repetitive biopsies from 10 patients with local recurrence in previously irradiated prostate which are selected for salvage HDR brachytherapy consisting of 3 x 10 Gy HDR. Biopsies were taken at 4 different time points (before (T0) and after the 1st fraction (T1); before the 2nd (T2) and 3rd fraction (T3) of the salvage treatment). PD-1/PD-L-1 expression was detected by immunohistochemical (IHC) analysis independently by 2 pathologists (XL, IS). The slides were scored semi-quantitatively for PD-1 : score 0: <1% tumor cells; 1: 1-5%; 2: >5%. PD-L-1 0: <1%; 11: 5%; 2: >5%. PD-L-1 status inflammatory cells: score 0: no staining; 1: <5%; 2: 5-50%; 3: >50%.
Immunophenotyping of tumor infiltration lymphocytes and stromal inflammatory cells was investigated.

Results

None of the patients showed PD-1 expression on the tumor cells or benign prostatic tissue at T0; however, PD-1-positive inflammatory cells were identified in at least four patients at each time point. At T0, there was no PD-L1 expression in tumor cells or inflammatory cells. After the first treatment (T1), PD-L-1 expression was identified on cancer cells in 3/10 patients. At T2-3, PD-L-1 positivity of tumor cells was observed in 9/10 patients. Inflammatory cells showed variable expression of PD-L-1 regardless of the specific time points. There was no association between PD-1/PD-L-1 and Gleason score.
The immunophenotype of inflammatory cells did not show significant differences when compared to the lymphoid subpopulations in all time points. Inflammatory infiltrate consisted mainly of CD4-positive T-lymphocytes as compared with CD20-positive B-lymphocytes. The CD4/CD8 ratio’s were respectively 0.92, 0.75, 0.67, and 1.14 for each time point, and were no significant different between the time points (p=0,2).

Conclusion

Increased PD-L-1 immune expression is induced by HDR-brachytherapy in prostate cancer. Further analyses of the infiltrating T-cells will be presented.