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Digital image analysis improves precision of PD‐L1 scoring in cutaneous melanoma

Indica Labs / Publications  / Digital image analysis improves precision of PD‐L1 scoring in cutaneous melanoma

Digital image analysis improves precision of PD‐L1 scoring in cutaneous melanoma

Viktor H. Koelzer, Aline Gisler, Jonathan C. Hanhart, Johannes Griss, Stephan N. Wagner, Niels Willi, Gieri Cathomas, Melanie Sachs, Werner Kempf, Daniela S. Thommen, Kirsten D. Mertz

Nature Medicine | First published April 16th, 2018 | DOI https://doi.org/10.1111/his.13528

Abstract

Aims
Immune checkpoint inhibitors have become a successful treatment in metastatic melanoma. The high response rates in a subset of patients suggest that a sensitive companion diagnostic test is required. The predictive value of programmed death ligand 1 (PD‐L1) staining in melanoma has been questioned due to inconsistent correlation with clinical outcome. Whether this is due to predictive irrelevance of PD‐L1 expression or inaccurate assessment techniques remains unclear. The aim of this study was to develop a standardised digital protocol for the assessment of PD‐L1 staining in melanoma and to compare the output data and reproducibility to conventional assessment by expert pathologists.

Methods and results
In two cohorts with a total of 69 cutaneous melanomas, a highly significant correlation was found between pathologist‐based consensus reading and automated PD‐L1 analysis (r = 0.97, P < 0.0001). Digital scoring captured the full diagnostic spectrum of PD‐L1 expression at single cell resolution. An average of 150 472 melanoma cells (median 38 668 cells; range = 733–1 078 965) were scored per lesion. Machine learning was used to control for heterogeneity introduced by PD‐L1‐positive inflammatory cells in the tumour microenvironment. The PD‐L1 image analysis protocol showed excellent reproducibility (r = 1.0, P < 0.0001) when carried out on independent workstations and reduced variability in PD‐L1 scoring of human observers. When melanomas were grouped by PD‐L1 expression status, we found a clear correlation of PD‐L1 positivity with CD8‐positive T cell infiltration, but not with tumour stage, metastasis or driver mutation status.

Conclusion
Digital evaluation of PD‐L1 reduces scoring variability and may facilitate patient stratification in clinical practice.

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Digital image analysis improves precision of PD‐L1 scoring in cutaneous melanoma

Indica Labs / Publications  / A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade

A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade

Daniela S. Thommen, Viktor H. Koelzer, Petra Herzig, Andreas Roller, Marcel Trefny, Sarah Dimeloe, Anna Kiialainen, Jonathan Hanhart, Catherine Schill, Christoph Hess, Spasenija Savic Prince, Mark Wiese, Didier Lardinois, Ping-Chih Ho, Christian Klein, Vaios Karanikas, Kirsten D. Mertz, Ton N. Schumacher & Alfred Zippelius

Nature Medicine | Published June 11th, 2018 | DOI https://doi.org/10.1038/s41591-018-0057-z

Abstract

Evidence from mouse chronic viral infection models suggests that CD8+T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression levels. We compared transcriptional, metabolic and functional signatures of intratumoral CD8+ T lymphocyte populations with high (PD-1T), intermediate (PD-1N) and no PD-1 expression (PD-1) from non-small-cell lung cancer patients. PD-1T T cells showed a markedly different transcriptional and metabolic profile from PD-1N and PD-1 lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1T lymphocytes were impaired in classical effector cytokine production, they produced CXCL13, which mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1T cells was strongly predictive for both response and survival in a small cohort of non-small-cell lung cancer patients treated with PD-1 blockade. The characterization of a distinct state of tumor-reactive, PD-1-bright lymphocytes in human cancer, which only partially resembles that seen in chronic infection, provides potential avenues for therapeutic intervention.

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