Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy

Authors: Xin Hong, Ryan J. Sullivan, Mark Kalinich, Tanya T. Kwan, Anita Giobbie‐Hurder, Shiwei Pan, Joseph A. LiCausi, John Milner, Linda T. Nieman, Ben S. Wittner, Uyen Ho, Tianqi Chen, Ravi Kapur, Donald P. Lawrence, Keith T. Flaherty, Lecia V. Sequist, Sridhar Ramaswamy, David T. Miyamoto, Michael S. Lawrence, Mehmet Toner, Kurt J. Isselbacher, Shyamala Maheswaran, Daniel A. Haber - Proceedings of the National Academy of Sciences, PNAS 2018 cited by 130

Significance Identifying predictive biomarkers of therapeutic response for melanoma patients treated with immune checkpoint inhibitors is a major challenge. By combining microfluidic enrichment for melanoma circulating tumor cells (CTCs) together with RNA-based droplet digital PCR quantitation, we have established a highly sensitive and robust platform for noninvasive, blood-based monitoring of tumor burden. Serial monitoring of melanoma patients treated with immune checkpoint inhibitors shows rapid changes in CTC score, which precede standard clinical assessment and are highly predictive of long-term clinical outcome. Early on-treatment digital monitoring of CTC dynamics may thus help identify patients likely to benefit from immune checkpoint inhibition therapy.