David Barbie, Professor at Dana-Farber Cancer Institute, shared on LinkedIn:
“Very proud of this work led by Koji Haratani, my stellar post-doctoral fellow and advanced clinical fellow in our Lowe Center for Thoracic Oncology.
This study was conducted in close collaboration with Ellis Reinherz and his team, who have taught us a great deal about fundamental T cell immunology and the importance of physically validating endogenous neoantigen display. Ellis is a legend in the field, having first identified CD4 and CD8 with Stu Schlossman, and then later being the first to purify and describe the physical structure of the human TCR itself in his own laboratory.
Thanks to the identification of a novel p53 neopitope and TCR, we discovered ERAP1 upregulation/hyperactivation as a key mechanism of human tumor immune evasion. In a manner complementary to unleashing STING-IFN signaling, ERAP inhibition can unleash display of overtrimmed truncal neopitopes, priming established tumors for immunologic destruction.”
Title: Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection
Authors: Koji Haratani, Bruce Reinhold, Jonathan S. Duke-Cohan, Caroline G. Fahey, Kemin Tan, Robert J. Mallis, Alexander Gusev, Kenneth L. Kehl, Jia Luo, Allyson Karmazyn, Elizabeth L. Holliday, Daniel J. Masi, Katarzyna J. Zienkiewicz, Connor J. Hennessey, Rafael B. Blasco, Tran C. Thai, Grace M. Gibbons, Sophie Kivlehan, Patrick Lizotte, Cloud P. Paweletz, Andrew J. Aguirre, Keith L. Ligon, Roberto Chiarle, Matthew J. Lang, David A. Barbie, Ellis L. Reinherz.
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