A digital single-molecule nanopillar SERS platform for predicting and monitoring immune toxicities in immunotherapy

• Published in: Nature communications Vol. 12; no. 1; pp. 1087 - 12
• Main Authors: Li, Junrong, Wuethrich, Alain, Sina, Abu A. I., Cheng, Han-Hao, Wang, Yuling, Behren, Andreas, Mainwaring, Paul N., Trau, Matt
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.02.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 140/133; 631/61/350; 639/301/357/537; 639/301/930/527/1821; 692/699/67/1059/2325; 9/10; Biomarkers; Cancer; Chemokine CX3CL1 - immunology; Chemokine CX3CL1 - metabolism; Cohort Studies; Cytokines; Cytokines - immunology; Cytokines - metabolism; Granulocyte Colony-Stimulating Factor - immunology; Granulocyte Colony-Stimulating Factor - metabolism; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Health services; Humanities and Social Sciences; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - immunology; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Immunotherapy - methods; Inflammation; Inhibitors; Ipilimumab - adverse effects; Ipilimumab - immunology; Ipilimumab - therapeutic use; Melanoma; Melanoma - immunology; Melanoma - metabolism; Melanoma - therapy; Microscopy, Confocal - methods; Monitoring; Monitoring, Immunologic - methods; multidisciplinary; Patients; Pilot Projects; Reproducibility of Results; Science; Science (multidisciplinary); Spectrum Analysis, Raman - methods; Telemedicine; Toxicity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21431-w

The introduction of immune checkpoint inhibitors has demonstrated significant improvements in survival for subsets of cancer patients. However, they carry significant and sometimes life-threatening toxicities. Prompt prediction and monitoring of immune toxicities have the potential to maximise the benefits of immune checkpoint therapy. Herein, we develop a digital nanopillar SERS platform that achieves real-time single cytokine counting and enables dynamic tracking of immune toxicities in cancer patients receiving immune checkpoint inhibitor treatment - broader applications are anticipated in other disease indications. By analysing four prospective cytokine biomarkers that initiate inflammatory responses, the digital nanopillar SERS assay achieves both highly specific and highly sensitive cytokine detection down to attomolar level. Significantly, we report the capability of the assay to longitudinally monitor 10 melanoma patients during immune inhibitor blockade treatment. Here, we show that elevated cytokine concentrations predict for higher risk of developing severe immune toxicities in our pilot cohort of patients. There is a clinical need to monitor immune-related toxicities of immune checkpoint blockade therapy. Here, the authors develop a digital SERS platform for multiplexed single cytokine counting to track immune-toxicities and demonstrate the ability to use pre-screening to identify patients at higher risk.