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