Pan-cancer analysis reveals distinct clinical, genomic, and immunological features of the immune checkpoint family in acute myeloid leukemia.

Leukocyte immunoglobulin (Ig)-like receptor Bs (s), a family of type I transmembrane glycoproteins, are known to inhibit immune activation. Here, we comprehensively evaluated the molecular, prognostic, and immunological characteristics of members in a broad spectrum of cancer types, focusing on their roles in acute myeloid leukemia (AML). We showed that s were significantly dysregulated in a number of cancers and were associated with immune-inhibitory phenotypes. Clinically, high expression of - predicted poor survival in six independent AML cohorts. Genetically, was associated with more mutational events than other members, and multiple genes involved in immune activation were deleted in patients. Epigenetically, was significantly hypomethylated and marked by MLL-associated histone modifications in AML. Immunologically, s were positively associated with monocytic cells, including M2 macrophages, but were negatively associated with tumor-suppressive CD8 T cells. Importantly, patients with higher expression generally showed a better response to immune checkpoint blockade (ICB) in five independent immunotherapy cohorts. Our findings reveal critical immunological and clinical implications of s in AML and indicate that s may represent promising targets for immunotherapy of AML.