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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

4483 - Assessment of PD-1/PD-L1 colocalization in hepatocellular carcinoma (HCC) using bright-field double labeling and quantitative digital image analysis

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Thomas Mrowiec

Citation

Annals of Oncology (2018) 29 (suppl_8): viii670-viii682. 10.1093/annonc/mdy304

Authors

T. Mrowiec1, F. Wilm2, E. Frick-Krieger2, M. Silva2, L. Terracciano3, I. Dussault4, C. Ihling2

Author affiliations

  • 1 Clinical Biomarkers & Cdx Department, Merck KGaA, 64293 - Darmstadt/DE
  • 2 Clinical Biomarkers & Cdx Department, Merck KGaA, Darmstadt/DE
  • 3 Department Of Pathology,, University of Basel, Basel/CH
  • 4 Clinical Biomarkers, Immuno-oncology, EMD Serono, Billerica/US
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Resources

Abstract 4483

Background

Tumors may suppress host defenses by activating immune checkpoints (eg, the programed cell death [PD-1/PD-L1] pathway). Colocalization (CL) is a requirement for PD-1/PD-L1 interaction. PD-1/PD-L1 CL in tissue sections, as determined by immunohistochemistry (IHC), may be an indicator of PD-L1/PD-1 pathway activity.

Methods

We assessed CL of PD-L1 and PD-1 in situ by applying a novel duplex bright-field IHC technique on 49 formalin-fixed, paraffin-embedded HCC samples using digital image analysis (DIA; Definiens Tissue Studio®) to determine the percentage of single PD-1+ and PD-L1+ cells, PD-L1/PD-1 double-labeled cells, and PD-1+ cells adjacent to ≥ 1 PD-L1+ cells.

Results

All cases showed typical HCC morphology (low- to high-grade trabecular [4/49], pseudoglandular [1/49], solid [40/49], clear cell [2/49], or desmoplastic [2/49]). PD-L1 was largely observed in immune cell infiltrates. On average, 2.6% ± 3.6% (median, 1.5%) of the cells (immune + tumor) within the tumor area were PD-1+, and 4.3% ± 5.5% (median, 1.9%) were PD-L1+. There was considerable variation among samples in the number of PD-1+ (range, 0.05%-21.2%) and PD-L1+ (range, 0.2%-30.3%) cells. In 18/49 cases (37%), the number of PD-1+ cells exceeded the number of PD-L1+ cells; in 31/49 cases (63%), the number of PD-L1+ cells exceeded the number of PD-1+ cells. PD-1/PD-L1 double-stained cells were present in 31/49 cases (63%), and 1.6% ± 4.1% (median, 0.13%) of the cells were double labeled, with considerable intersample variation (range, 0.5%-22.9%). Finally, 10.5% ± 8.03% (median, 9.4%) of PD-1+ cells were in the immediate vicinity of a PD-L1+ cell (range, 1.1%-43.3%).

Conclusions

By combining a novel duplex bright-field IHC technique with DIA, we quantitated the number/distribution of PD-1+ and PD-L1+ cells in HCC. Variation in the numbers of PD-1+ and PD-L1+ cells, and PD-1+ cells with ≥1 PD-L1+ adjacent cells, in HCC was seen. Future studies can use these techniques to explore the predictive potential of PD-L1/PD-1 expression in patients who are being considered for immunotherapy. Our proof of concept results suggest that the methods may also be applied for other tumors.

Clinical trial identification

Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany.

Funding

Merck KGaA, Darmstadt, Germany.

Editorial Acknowledgement

Medical writing support was provided by ClinicalThinking, and was funded by Merck KGaA, Darmstadt, Germany.

Disclosure

T. Mrowiec, F. Wilm, E. Frick-Krieger, C. Ihling: Employment: Merck KGaA. M. Silva: Employment: Merck KGaA; Equity ownership: Merck KGaA. L. Terracciano: Consultancy: Merck KGaA. I. Dussault: Employment: EMD Serono.

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