Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade

Sneha Berry; Nicolas A Giraldo; Benjamin F Green; Tricia R Cottrell; Julie E Stein; Elizabeth L Engle; Haiying Xu; Aleksandra Ogurtsova; Charles Roberts; Daphne Wang; Peter Nguyen; Qingfeng Zhu; Sigfredo Soto-Diaz; Jose Loyola; Inbal B Sander; Pok Fai Wong; Shlomit Jessel; Joshua Doyle; Danielle Signer; Richard Wilton; Jeffrey S Roskes; Margaret Eminizer; Seyoun Park; Joel C Sunshine; Elizabeth M Jaffee; Alexander Baras; Angelo M De Marzo; Suzanne L Topalian; Harriet Kluger; Leslie Cope; Evan J Lipson; Ludmila Danilova; Robert A Anders; David L Rimm; Drew M Pardoll; Alexander S Szalay; Janis M Taube

doi:10.1126/science.aba2609

Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade

Science. 2021 Jun 11;372(6547):eaba2609. doi: 10.1126/science.aba2609.

Authors

Sneha Berry^#^{1

2

3}, Nicolas A Giraldo^#⁴, Benjamin F Green^#^{1

2

5}, Tricia R Cottrell⁴, Julie E Stein⁴, Elizabeth L Engle^{1

2

5}, Haiying Xu^{1

2

5}, Aleksandra Ogurtsova^{1

2

5}, Charles Roberts^{2

5}, Daphne Wang⁵, Peter Nguyen⁵, Qingfeng Zhu⁴, Sigfredo Soto-Diaz^{2

5}, Jose Loyola^{2

5}, Inbal B Sander⁵, Pok Fai Wong⁶, Shlomit Jessel⁶, Joshua Doyle^{7

8}, Danielle Signer⁵, Richard Wilton^{7

8}, Jeffrey S Roskes^{7

8}, Margaret Eminizer^{7

8}, Seyoun Park^{1

9}, Joel C Sunshine⁵, Elizabeth M Jaffee^{1

2

3}, Alexander Baras⁴, Angelo M De Marzo^{3

4}, Suzanne L Topalian^{2

10}, Harriet Kluger¹¹, Leslie Cope^{1

2

12}, Evan J Lipson^{1

2

3}, Ludmila Danilova^{1

2

12}, Robert A Anders^{1

2

4}, David L Rimm⁶, Drew M Pardoll^{1

2

3}, Alexander S Szalay^#^{1

7

8}, Janis M Taube^#^{13

2

4

5}

Affiliations

¹ The Mark Foundation Center for Advanced Genomics and Imaging, Johns Hopkins University, Baltimore, MD 21287, USA.
² Bloomberg~Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
³ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
⁴ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
⁵ Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
⁶ Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
⁷ Department of Astronomy and Physics, Johns Hopkins University, Baltimore, MD 21218, USA.
⁸ Institute for Data Intensive Engineering and Science, Johns Hopkins University, Baltimore, MD 21218, USA.
⁹ Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
¹⁰ Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
¹¹ Division of Medical Oncology, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
¹² Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
¹³ The Mark Foundation Center for Advanced Genomics and Imaging, Johns Hopkins University, Baltimore, MD 21287, USA. [email protected].

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antigens, CD / analysis
Antigens, Differentiation, Myelomonocytic / analysis
Antineoplastic Agents, Immunological / therapeutic use*
B7-H1 Antigen / analysis
Biomarkers, Tumor / analysis*
CD8 Antigens / analysis
Female
Fluorescent Antibody Technique*
Forkhead Transcription Factors / analysis
Humans
Immune Checkpoint Proteins / analysis
Macrophages / chemistry
Male
Melanoma / chemistry
Melanoma / drug therapy*
Melanoma / immunology
Melanoma / pathology
Middle Aged
Prognosis
Programmed Cell Death 1 Receptor / analysis
Programmed Cell Death 1 Receptor / antagonists & inhibitors*
Progression-Free Survival
Receptors, Cell Surface / analysis
SOXE Transcription Factors / analysis
Single-Cell Analysis
T-Lymphocyte Subsets / chemistry
T-Lymphocyte Subsets / immunology
Treatment Outcome
Tumor Microenvironment

Substances

Antigens, CD
Antigens, Differentiation, Myelomonocytic
Antineoplastic Agents, Immunological
B7-H1 Antigen
Biomarkers, Tumor
CD163 antigen
CD274 protein, human
CD8 Antigens
FOXP3 protein, human
Forkhead Transcription Factors
Immune Checkpoint Proteins
PDCD1 protein, human
Programmed Cell Death 1 Receptor
Receptors, Cell Surface
SOX10 protein, human
SOXE Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding