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Science ; 372(6547)2021 06 11.
Article in English | MEDLINE | ID: mdl-34112666

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-1low/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.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Biomarkers, Tumor/analysis , Fluorescent Antibody Technique , Melanoma/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , B7-H1 Antigen/analysis , CD8 Antigens/analysis , Female , Forkhead Transcription Factors/analysis , Humans , Immune Checkpoint Proteins/analysis , Macrophages/chemistry , Male , Melanoma/chemistry , Melanoma/immunology , Melanoma/pathology , Middle Aged , Prognosis , Programmed Cell Death 1 Receptor/analysis , 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
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