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.