Research ArticleCancer

Pediatric patients with acute lymphoblastic leukemia generate abundant and functional neoantigen-specific CD8+ T cell responses

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Science Translational Medicine  26 Jun 2019:
Vol. 11, Issue 498, eaat8549
DOI: 10.1126/scitranslmed.aat8549

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Challenging immunogenicity assumptions

Cancers with lower mutation rates, such as pediatric acute lymphoblastic leukemia (ALL), have not shown high immunotherapy response rates, possibly because there are fewer neoepitopes for T cells to recognize. To better understand antitumor responses, Zamora et al. examined samples from pediatric patients with ALL. They predicted peptide neoepitopes that could bind patients’ HLA for presentation to T cells and generated tetramers. Somewhat surprisingly, almost all of the predicted peptides were recognizable by patient T cells and induced functional responses in vitro. They detected immunodominance hierarchies and some shared recognition derived from a common ETV6-RUNX1 fusion in tumors. This study shows that low mutation burden tumors such as pediatric ALL should not be assumed to be immunogenically silent and could respond to checkpoint blockade or other T cell–targeted therapies.

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