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

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.
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