Ilyas Sahin, Medical Oncologist at Massachusetts General Hospital, shared on X:
”Why do T-cell therapies work in blood cancers but struggle in solid tumors?
A Nature study from Julia Carnevale’s lab, led by Qi Liu (Gladstone Institute, UC San Francisco), ran genome-wide CRISPR screens on human T cells inside tumors, not in a dish.
Two especially interesting hits emerged, each blocking a different step:
P2RY8 keeps T cells from getting into the tumor. GNAS is where many of the tumor’s “stand down” signals converge.
Delete GNAS, and T cells become resistant to several of those suppressive cues at once.
Delete both: in one preclinical model, 4 of 6 mice cleared their tumors, vs 1 of 6 with GNAS deletion alone.
A clever demonstration that the tumor itself can help reveal what to engineer into better T-cell therapies.”
Title: In vivo genome-wide CRISPR screens of human T cells in solid tumours
Authors: Qi Liu, Peixin Amy Chen, Esha Urs, Shimin Zhang, Maya M. Arce, Charlotte H. Wang, Jun Yan, Vinh Q. Nguyen, Zhongmei Li, Jin Seo, Nupura Kale, Fanglue Peng, Yikai Luo, Laine Goudy, Taylor N. LaFlam, Haixia Zhong, Chandrima Modak, Emma Dann, Jae Hyung Jung, Amanda Kirane, Allison Betof Warner, Boi Bryant Quach, Zinaida Good, Brian R. Shy, Eric Shifrut, Sagar P. Bapat, Greg M. Allen, Justin Eyquem, Katherine Fuh, Stacie E. Dodgson, Jason G. Cyster, Alexander Marson, Julia Carnevale
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