Silvia Deaglio, MD, PhD, of the University of Turin, Turin, Italy, outlines the molecular and microenvironmental factors that lead to immunodysfunction in chronic lymphocytic leukemia (CLL). Immune checkpoint inhibitors have limited success in treating CLL due to dysfunction of multiple immune checkpoints. Dr Deaglio describes the T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM domain) (TIGIT), which has recently been identified as a novel NK inhibitory receptor associated with cell exhaustion and dysfunction. This interview took place during the ninth annual meeting of the Society of Hematologic Oncology (SOHO 2021) congress.