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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

1297 - Characterization of PD-L1, CD8, CD3, CD68 and PanCK in Tumor Microenvironment of Gl Tract Tumors with respect to Patients’ Mismatch Repair Status and Anti-PD-1 Treatment Outcome using 5Plex IHC and Whole Slide Image Analysis

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Wenjun Zhang

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

W. Zhang1, M. Khojasteh2, A. Hubbard3, J. Martin4, X. Wang4, S. Kamthamraju3, J.L. Munoz-Rodriguez3, D. Jiang5, Z. Cai6, J. Li6, R. Anders7, L. Diaz8, L. Pestic-Dragovich3, L. Tang3

Author affiliations

  • 1 Cdx Pharma Service, Roche Tissue Diagnostics - USA, 85737 - Tucson/US
  • 2 Digital Pathology, Roche Tissue Diagnostics USA, 94043 - Mountain View/US
  • 3 Cdx Pharma Service, Roche Tissue Diagnostics - USA, 85755 - Tucson/US
  • 4 Digital Pathology, Roche Tissue Diagnostics - USA, 94043 - Mountain View/US
  • 5 R&d, Roche Tissue Diagnostics - USA, 85755 - Tucson/US
  • 6 Biostatistics, Roche Tissue Diagnostics - USA, 85755 - Tucson/US
  • 7 Pathology, John Hopskin University Hospital, 21287 - Baltimore/US
  • 8 Division Of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York City/US
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Resources

Abstract 1297

Background

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. However, not all patients with mismatch repair deficiency respond to the PD-1 blockade treatment. To understand the different responses, we evaluated tumor micro-environment such as PD-L1 expression in relationship with tumor infiltrating immune cells.

Methods

FL multiplex IHC for PD-L1, CD8, CD3, CD68, and pan-cytokeratin (panCK) on BenchMark ULTRA instrument stained 54 pre-pembrolizumab treatment patient resection and biopsy specimens including pancreatic, colorectal and cholangiocarcinoma. 17 are mismatch-repair proficient (13 PD, 3 SD, and 1 CR) and 37 deficient (5 PD, 10 SD, 9 CR, and 13 PR). Whole slide images by Zeiss AXIO Z1 were analyzed with in-house dPath automated algorithm. PD-L1+/- T-cells (CD3+), cytotoxic T-cells (CD3+ and CD8+), T helper cells (CD3+ and CD8-), macrophages (CD68+), and tumor cells (panCK+) were identified. Fractions of PD-L1+ phenotypes, area density and spatial relationships of phenotypes in pathologist-annotated tumor/peritumor regions, the panCK+ epithelial tumor and panCK- stroma were computed.

Results

Random forest modelling, logistic regression and Relieff feature selection followed by quadrant discriminant analysis were used to assess the relationship of multiplex IHC readouts to anti-PD-1 treatment responses. Different groupings were used, e.g. PR + CR vs. SD + PD, and PR + CR + SD vs. PD, etc. Fraction of PD-L1+ macrophages and fraction of PD-L1+ T helper cells in tumor region, stroma, and epithelial tumor were identified most important features. Mpx IHC achieves 89% accuracy over 70% with mismatch repair status alone.

Conclusions

Multiplex IHC together with automated image analysis provides a tool to evaluate multiple biomarkers and their special relationships in the tumor micro-environment. In a cohort of 54 patient specimens, exploratory analysis of multiplex IHC data suggests that the knowledge of PD-L1 expression on various immune cell phenotypes aids in better predicting response to anti-PD-1 therapy compared to mismatch repair status alone.

Clinical trial identification

Legal entity responsible for the study

Roche Diagnostics/Ventana Medical Systems, Inc.

Funding

Roche Diagnostics/Ventana Medical Systems, Inc.

Editorial Acknowledgement

Disclosure

W. Zhang, M. Khojasteh, A. Hubbard, X. Wang, J.L. Munoz-Rodriguez, D. Jiang, Z. Cai, J. Li, L. Pestic-Dragovich, L. Tang: Employee: Roche Diagnostics. J. Martin, S. Kamthamraju: Contractor employee: Roche Diagnostics. R. Anders: Financial relationships: Merck, BMS, 5 Prime Therapeutics, FLX Bio, Adaptive Biotech. L. Diaz: Founder: Personal Genome Diagnostics, PapGene, PagerBox.

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