Impact of genetic alterations on the tumor microenvironment. The major mechanisms of 16p13.13 gene rearrangements leading to CIITA gene fusions and 9p24.1 amplification. These mechanisms involve down-regulation of MHC class II and up-regulation of PD-1 ligands, leading to an imbalance of T-cell receptor versus costimulatory signaling. Functional consequences for the tumor microenvironment encompass induction of T-cell anergy, apoptosis, and skewed differentiation toward regulatory T cells. Orange triangles indicate chromosomal break (B). ER indicates endoplasmic reticulum.