Chromosome instability and aneuploidy as context-dependent activators or inhibitors of antitumor immunity

Abstract

Chromosome instability (CIN) and its major consequence, aneuploidy, are hallmarks of human cancers. In addition to imposing fitness costs on tumor cells through several cell-intrinsic mechanisms, CIN/aneuploidy also provokes an antitumor immune response. However, as the major contributor to genomic instability, intratumor heterogeneity generated by CIN/aneuploidy helps tumor cells to evolve methods to overcome the antitumor role of the immune system or even convert the immune system to be tumor-promoting. Although the interplay between CIN/aneuploidy and the immune system is complex and context-dependent, understanding this interplay is essential for the success of immunotherapy in tumors exhibiting CIN/aneuploidy, regardless of whether the efficacy of immunotherapy is increased by combination with strategies to promote CIN/aneuploidy or by designing immunotherapies to target CIN/aneuploidy directly.