Identification of immune evasion mechanisms in myeloid leukemias by mapping natural killer cells by single-cell transcriptomics

Abstract

Advances in immunotherapy have already been achieved with checkpoint inhibitors to enhance T cell responses such as inhibition of PD-1/PDL-1 in solid tumors and lymphoproliferative diseases, with promising results, and more scarce data from clinical trials in myeloid leukemias, as well as with Genetic Engineering of T lymphocytes (CAR-T cell therapy). However, for myeloid diseases, this therapy still faces great limitations due to the difficulty of targeting specific leukemic antigens that are not present in normal cells. Leukemic initiating cells are resistant to the immune system, either by deficiency of ligands at the level of the tumor cell, or by deficiency of receptors or molecules essential for the performance of effector cells. In this context, a deep characterization of innate lymphoid cells, in particular Natural Killer (NK) cells, deserves investigation, and can be the scientific base for developing strategies to reestablish the antitumoral immunity, especially for myeloid malignancies, yet unfortunately rarely curable. (AU)