1. Fluorogenic Granzyme A substrates enable real-time imaging of adaptive immune cell activity
- Author
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Gobierno de Aragón, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Medical Research Council (UK), Cancer Research UK, European Research Council, Mendive-Tapia, Lorena [0000-0002-3406-5203], Kitamura, Takanori [0000-0003-2032-3918], Samarakoon, Youhani [0000-0002-9845-4232], Roberts, Edward W. [0000-0002-8229-1715], Arias, Maykel [0000-0002-9730-2210], Pardo, Julián [0000-0003-0154-0730], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Cheng, Zhiming, Thompson, Emily J., Mendive-Tapia, Lorena, Scott, Jamie I., Benson, Sam, Kitamura, Takanori, Senán Salinas, Ana, Samarakoon, Youhani, Roberts, Edward W., Arias, Maykel, Pardo, Julián, Gálvez Buerba, Eva Mª, Gobierno de Aragón, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Medical Research Council (UK), Cancer Research UK, European Research Council, Mendive-Tapia, Lorena [0000-0002-3406-5203], Kitamura, Takanori [0000-0003-2032-3918], Samarakoon, Youhani [0000-0002-9845-4232], Roberts, Edward W. [0000-0002-8229-1715], Arias, Maykel [0000-0002-9730-2210], Pardo, Julián [0000-0003-0154-0730], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Cheng, Zhiming, Thompson, Emily J., Mendive-Tapia, Lorena, Scott, Jamie I., Benson, Sam, Kitamura, Takanori, Senán Salinas, Ana, Samarakoon, Youhani, Roberts, Edward W., Arias, Maykel, Pardo, Julián, and Gálvez Buerba, Eva Mª
- Abstract
Cytotoxic immune cells, including T lymphocytes (CTLs) and natural killer (NK) cells, are essential components of the host response against tumors. CTLs and NK cells secrete granzyme A (GzmA) upon recognition of cancer cells; however, there are very few tools that can detect physiological levels of active GzmA with high spatiotemporal resolution. Herein, we report the rational design of the near-infrared fluorogenic substrates for human GzmA and mouse GzmA. These activity-based probes display very high catalytic efficiency and selectivity over other granzymes, as shown in tissue lysates from wild-type and GzmA knock-out mice. Furthermore, we demonstrate that the probes can image how adaptive immune cells respond to antigen-driven recognition of cancer cells in real time.
- Published
- 2022