Rizwan Haq: New mechanism of resistance to immunotherapy in melanoma
Rizwan Haq, Melanoma physician-scientist at Dana-Farber Cancer Institute, shared a post on X about a paper he co-authored with colleagues published in Cancer Cell:
“Genomic mediators of acquired resistance to immunotherapy in metastatic melanoma”
Authors: Julia Schiantarelli, Mouadh Benamar, Jihye Park, Eliezer Van Allen, Rizwan Haq et al.
“Our paper on a new mechanism of resistance to immunotherapy in melanoma is now in print Cancer Cell with the Van Allen lab.
Although some patients with metastatic melanoma experience durable responses to immune checkpoint inhibitors, most exhibit intrinsic or acquired resistance to these therapies.
Over several years, we collected matched pre-treatment and post-resistance tumor biopsies in patients with metastatic melanoma who exhibited heterogeneous ICI responses to nominate additional mediators of acquired resistance.
Strikingly, we found resistance-associated mutations in SEC24C and SEC24D in 3 patients. Melanoma cells engineered to express the SEC24C mutations observed in patients exhibit diminished STING signalling, including decreased Type I interferon production, antigen presentation and a reduced capacity to activate cytotoxic T cells.
The project was only possible because of collaboration with the Van Allen lab, talented co-first authors Julia Schiantarelli, Mouadh Benamar, and Jihye Park. I am also grateful to patients who donated biopsy material and funding sources, including Melanoma Research Alliance, and Dana-Farber Cancer Institute.”
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