PerspectiveCANCER IMMUNOLOGY

Chromosomal chaos silences immune surveillance

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Science  20 Jan 2017:
Vol. 355, Issue 6322, pp. 249-250
DOI: 10.1126/science.aam5331

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Summary

Not all cancers, and not all individuals with the same cancer type, respond equally to immunotherapy—the use of antibodies to block so-called immune checkpoints in T cells—thereby unleashing immune responses against tumor cells. This can be partially explained by nonsynonymous mutations, which can create neoantigen epitopes that induce T cell responses against cancer cells (1). However, such mutations scattered throughout the genome may or may not activate the immune system, and if they do, their effect wanes over time. Is there a role for other genomic abnormalities of cancer cells in immune surveillance beyond the generation of neoantigens? On page 261 of this issue, Davoli et al. (2) propose that structural abnormalities in chromosomes, including variation in the number of chromosome copies (aneuploidy), adversely affect immune cell action against the tumor.