Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade
- 11 June 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 372 (6547), 1166-+
- https://doi.org/10.1126/science.aba2609
Abstract
Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well as distinct expression patterns of immunoregulatory molecules. Here, we introduce a comprehensive platform for multispectral imaging and mapping of multiple parameters in tumor tissue sections with high-fidelity single-cell resolution. Image analysis and data handling components were drawn from the field of astronomy. Using this "AstroPath" whole-slide platform and only six markers, we identified key features in pretreatment melanoma specimens that predicted response to anti-programmed cell death-1 (PD-1)-based therapy, including CD163(+)PD-L1(-) myeloid cells and CD8(+)FoxP3(+)PD-1(low/mid) T cells. These features were combined to stratify long-term survival after anti-PD-1 blockade. This signature was validated in an independent cohort of patients with melanoma from a different institution.Keywords
Funding Information
- National Institutes of Health
- National Cancer Institute
- Bristol-Myers Squibb
- Melanoma Research Alliance
- Harry J. Lloyd Charitable Trust
- Sidney Kimmel Comprehensive Cancer Center
- Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
- the Emerson Collective
- Moving for Melanoma of Delaware
- the Barney Family Foundation
- The Laverna Hahn Charitable Trust
- The Mark Foundation
This publication has 45 references indexed in Scilit:
- Comparison of Biomarker Modalities for Predicting Response to PD-1/PD-L1 Checkpoint BlockadeJAMA Oncology, 2019
- Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumabJournal for ImmunoTherapy of Cancer, 2018
- Effect of neoadjuvant chemotherapy on the immune microenvironment in non–small cell lung carcinomas as determined by multiplex immunofluorescence and image analysis approachesJournal for ImmunoTherapy of Cancer, 2018
- Quantitative Analysis of Immune Infiltrates in Primary MelanomaCancer Immunology Research, 2018
- Eight-Color Multiplex Immunohistochemistry for Simultaneous Detection of Multiple Immune Checkpoint Molecules within the Tumor MicroenvironmentThe Journal of Immunology, 2018
- Implications of the tumor immune microenvironment for staging and therapeuticsLaboratory Investigation, 2017
- Mismatch repair deficiency predicts response of solid tumors to PD-1 blockadeScience, 2017
- Multiparametric immune profiling in HPV– oral squamous cell cancerJCI Insight, 2017
- PD-1/PD-L1 inhibitorsCurrent Opinion in Pharmacology, 2015
- Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancerScience, 2015