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Francesca D. Ciccarelli: A constitutive interferon-high immunophenotype defines response to IO in colorectal cancer
Francesca D. Ciccarelli, Professor of Molecular Biology at University of Milan, posted on LinkedIn about recent paper by Amelia Acha-Sagredo et al., titled “A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer” published on Cancer Cell by Cell Press.
Authors: Amelia Acha-Sagredo, Pietro Andrei, Kalum Clayton, Emma Taggart, Carlotta Antoniotti, Chloé A. Woodman, Hassnae Afrache, Constance Fourny, Maria Armero, Hafsa Kaja Moinudeen, Mary Green, Nisha Bhardwaj, Anna Mikolajczak, Maria Rodriguez-Lopez, Marg Crawford, Emma Connick, Steven Lim, Philip Hobson, Josep Linares, Ekaterina Ignatova, Francesca D. Ciccarelli
“Check out our latest study published in Cancer Cell by Cell Press!
Amelia Acha Sagredo meticulously separated out cancer epithelium and tumour stroma compartments from colorectal cancer patients via laser-capture microdissection to derive their transcriptomic profiles.
Kalum Clayton then compared the level of expression of several gene signatures between samples treated (dMMR CRC) or not (pMMR CRC) with immunotherapy. He found significantly more intra-epithelial infiltration of antigen-presenting macrophages, cytotoxic CD8 and NK cells in dMMR CRCs responding to treatment. These populations created an interferon-high local microenvironment.
To assess how the proximity of interferon-producing T cells impacted on cancer cells and macrophages, Pietro Andrei developed an approach for spatial transcriptomics data analysis leading to the identification of CD74 as marker of the interferon-high local microenvironment. With the help of Michele Mishto lab, Amelia and Emma Taggart confirmed these results in co-cultures of cancer and T cells.
Elisa Fontana and Manuel Rodriguez-Justo then helped us validate CD74 abundance as a marker of the local microenvironment conducive to response to immunotherapy. Most importantly, we saw high levels of CD74 also in pMMR CRCs treated with immunotherapy in clinical trials led by Chiara Cremolini.
This opens up to the development of a novel, TMB-independent and subtype-agnostic test for eligibility to immunotherapy!
Thanks to all colleagues who contributed and are not mentioned here, our scientific homes The Francis Crick Institute and Barts Cancer Institute (Queen Mary University of London) and our supporting agencies Cancer Research UK (CRUK), Cancer Research Horizons, Cancer Research UK City of London Centre and Barts Charity!
Looking forward to the next step!”
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