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Vienna, Austria

ESTRO 2023

Session Item

Immuno-radiobiology
Poster (Digital)
Radiobiology
HDR-brachytherapy increases PD-L-1 immune expression on prostate cancer (NCT04247217)
Ben Vanneste, Belgium
PO-2242

Abstract

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

Ben Vanneste1,2, 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.